Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.

BACKGROUND: The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS: This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS: One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS: HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.

[Hepatic MALT lymphoma associated with chronic hepatitis B in a patient on trial therapy of Entecavir and H. pylori eradication therapy - case report].

A 65-year-old woman with a history of chronic hepatitis B was referred to our hospital for the examination of abdominal lymphadenopathy and diffuse lesions in the liver. Endoscopic ultrasound-guided fine-needle aspiration biopsy and liver biopsy were performed, and mucosa-associated lymphoid tissue (MALT) lymphoma was found in both. Based on the results of various images, a diagnosis of primary hepatic MALT lymphoma, Ann Arbor classification stage IV was reached at. Entecavir administration, H. pylori eradication therapy, and chemotherapy were performed, and remission was induced. The tumor condition remained unchanged after H. pylori eradication therapy and Entecavir administration. Subsequently, she became symptomatic, so chemotherapy was performed, leading to remission. We herein report a case of hepatic MALT lymphoma associated with chronic hepatitis B.

IgA Vasculitis in an Oldest-old Patient Successfully Treated with Glucocorticoid.

A 94-year-old man was diagnosed with immunoglobulin A vasculitis (IgAV), and losartan was initiated. His renal function rapidly deteriorated over a month; therefore, methylprednisolone was administered intravenously for three days followed by oral prednisolone. Renal function improvement and both proteinuria and hematuria remission were observed within six months. Prednisolone tapering was completed at eight months. In this case, we monitored the patient carefully and started glucocorticoids as soon as the patient's renal function deteriorated. We were thus able to treat the patient with a relatively small dose of glucocorticoids in a short treatment period without any adverse events due to glucocorticoids.

Intestinal-type gastric dysplasia in Helicobacter pylori-naïve patients.

Gastric dysplasia and gastric cancer in Helicobacter pylori (Hp)-naïve patients usually exhibit a gastric phenotype, reflecting gastric mucosa without intestinal metaplasia (IM). We showed that intestinal-type gastric dysplasia (IGD) rarely occurs in the Hp-naïve stomach. In the last 10 years, we treated 1760 gastric dysplasia and gastric cancer patients, with 3.6% (63/1760) being Hp-naïve. Among these, ten were diagnosed with 14 IGDs and enrolled in this retrospective analysis. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We analyzed their endoscopic and microscopic features and patient demographics. Five men and five women aged 64 ± 21 years were included. WLE showed the depressed lesions mimicking a benign raised erosion in the prepyloric compartment. Multiple growths were confirmed in 30% (3/10) of patients. NBIME showed a near-regular microstructure and capillaries in 50% (7/14) of lesions with a gastritis-like appearance. Histologically, background mucosa was non-atrophic pyloric gland tissue, but 40.0% of samples (4/10) contained sporadic IM. Most of the lesions (8/14) were low-grade dysplasia, and others had a high-grade component, with one progressing to intramucosal carcinoma. The neoplastic surface was widely covered with foveolar epithelium in 57.1% (8/14). Immunohistochemically, neoplastic cells expressed CDX2 in all patients (14/14), MUC2 and CD10 in 92.9% (13/14), MUC5AC in 14% (2/14), and no expression of MUC6, showing an intestinal phenotype. Ki-67 was overexpressed with a mean labeling index of 58.3 ± 38.5%, and p-53 was overexpressed in 92.9% (13/14), regardless of the dysplastic grade. The IGD rarely occurs in Hp-naïve patients with distinctive clinicopathologic characteristics.

[Pyogenic granuloma in small intestine associated with Cowden's disease in a patient with gastrointestinal bleeding:a case report].

A 57-year-old female with a history of Cowden's disease was referred to our hospital because of black stool, loss of consciousness, and severe anemia. Upper and lower gastrointestinal endoscopy findings could not confirm the source of hemorrhage. Capsule endoscopy (CE) of the small intestine showed an active exudative hemorrhagic site near the ileum, although a definitive diagnosis was difficult. In a double balloon enteroscopy examination, it was difficult to observe the entire small intestine due to adhesions and the responsible lesion could not be confirmed, even when ink spots were applied to the deepest observation points through the mouth and anus. Hemostasis spontaneously occurred, and then anemia occurred again approximately 1 month later and a second CE examination was performed including passage of an ink stick through the oral side, which revealed an exudative elevated polyp with erosion and a white moss appearance in the ileum. Partial ileal resection was performed and pyogenic granuloma of the small intestine was the diagnosis. We report here a case of pyogenic granuloma of the small intestine associated with Cowden's disease.

Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.

[A case of long-term survival in stage IV squamous cell carcinoma of the anal canal with multidisciplinary treatment].

A 60-year-old female presented to our hospital with anal pain. Colonoscopy (CS) revealed a tumor in the anal canal, which was diagnosed as squamous cell carcinoma by biopsy. Computed tomography (CT) showed multiple liver metastases. From these findings, we diagnosed the anal tumor as stage IV squamous cell carcinoma of the anal canal. Although CS and CT indicated disappearance of the primary tumor and liver metastases following chemoradiotherapy, brain metastasis developed during the disease course and was treated with radiotherapy and surgical resection. Administration of S-1 as adjuvant chemotherapy was continued, and the patient has remained alive for approximately six years without recurrence. To the best of our knowledge, this case can be considered as having the longest-term survival in stage IV squamous cell carcinoma of the anal canal.

A Combined Deposition of Lanthanum and ß2-Microglobulin-Related Amyloid in the Gastroduodenal Mucosa of Hemodialysis-Dependent Patients: An Immunohistochemical, Electron Microscopic, and Energy Dispersive X-Ray Spectrometric Analysis.

Lanthanum carbonate (LC) is a new type of phosphate adsorbent used to treat patients with hyperphosphatemia caused by chronic kidney diseases. Recent studies have pointed out that lanthanum deposition can be found in the cytoplasm of histiocytes in the gastroduodenal mucosa of these patients. On the other hand, it is well known that patients on long-term hemodialysis can develop deposition of ß2-microglobulin-related amyloid (Aß2M) mainly around joints. However, involvement of the gastrointestinal tract by hemodialysis-associated amyloidosis has been thought to be rare, and therefore only Aß2M, if any, has been reported to accumulate in the vascular walls of the submucosa and muscularis propria. Thus, in contrast to AA amyloid, biopsy from gastrointestinal mucosa has long been considered to have little significance in detecting amyloid. We present unusual histologic findings on biopsy specimens taken from the gastroduodenal mucosa of 7 hemodialysis-dependent patients taking LC for more than a year. These findings were due to a combined deposition of lanthanum and ß2-microglobulin-related amyloid in the cytoplasm of histiocytes. The deposition of amyloid was confirmed by conventional histochemistry, immunohistochemistry, and transmission electron microscopy, and that of lanthanum by transmission electron microscopy and scanning electron microscopy/energy dispersive X-ray spectrometry. This is the first report of such a peculiar combined deposition of lanthanum and amyloid in the gastroduodenal mucosa of hemodialysis patients. Although the exact mechanism of combination and pathogenesis is unclear, we believe that histologic examination of the gastrointestinal mucosa should be considered in the careful follow-up and observation of hemodialysis patients taking LC.

[Liposarcoma of the Spermatic Cord : A Case Report and Review of the Literature].

A 92-year-old man had noticed enlargement of a mass in the right scrotum and inguinal region for nine months. The patient was introduced to our department for right testicular tumor. Physical examination showed an over fist-sized, hard mass in the right scrotum. Magnetic resonance imaging (MRI) showed the mass, which consisted of fatty and solid contents. In addition, MRI revealed a bladder tumor simultaneously. Computed tomography revealed no distant metastases. The patient underwent right high orchiectomy with the mass resection and transurethral resection of the bladder tumor (TURBT). Pathological examination revealed well- and dedifferentiated liposarcoma of the right spermatic cord, and urothelial cancer of the bladder. Liposarcoma of the spermatic cord is a rare neoplasm. To the best of our knowledge, the present case was the 114 th reported case and oldest in Japan.

[A case of chronic pancreatitis occurring in gastric aberrant pancreas poorly distinguishable from gastric aberrant pancreas ductal carcinoma].

A man in his 40s was referred to our hospital with abdominal pain. A gastric submucosal tumor (SMT) was diagnosed nine years previously, but the patient was lost to follow-up. Upon our evaluation, the SMT had enlarged, as demonstrated by esophagogastroduodenoscopy and abdominal computed tomography. Endoscopic ultrasonography revealed a hypoechoic and isoechoic mosaic mass, which primarily occupied the third and fourth layers of the gastric wall. Aspiration cytodiagnosis was performed, the results of which led to a suspicion of adenocarcinoma arising from gastric ectopic pancreas. Next, we conducted segmental gastrectomy. Pathological examination showed adiponecrosis, a pancreatic stone, chronic inflammatory cell infiltration, and fibrosis. Thus, the patient was diagnosed with chronic pancreatitis occurring in a gastric aberrant pancreas.

[A case of cavernous angioma at the convexity in the dura mater: characteristics of images in the literature].

We describe a rare case of cavernous angioma in the dura mater and discuss published MRI findings on similar cases. The patient was a 78-year-old woman who was referred to Shimane Prefectural Central Hospital with complaints of headaches. We were subsequently able to identify a tumor at the convexity in the dura mater. The tumor showed a high intensity on T2-weighted images and was heterogeneously enhanced on contrast-enhanced T1-weighted images. The maximum size of the tumor was 35 mm. Moreover, preoperative angiography showed a slight vascularity in the tumor. We performed surgery with the expectation of finding a meningioma, metastatic brain tumor, or another mesenchymal tumor. The tumor was dark and red, attached to the dura mater, and adhered to the arachnoid. However, we were able to peel the tumor away from the meninges and achieved a total removal of the mass, successfully cutting a fine feeding cortical artery. The patient was discharged without neurological defects 9 days after surgery;the pathological diagnosis was cavernous angioma. In conclusion, it is difficult to discern between meningioma and cavernous angioma in the dura mater. However, the specificity of high intensity on T2-weighted images is relatively high, and preoperative diagnosis can be determined by MRI and angiography findings.

Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report.

Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.

[A case of tumor progression after gamma knife radiosurgery for brain metastasis of thyroid papillary carcinoma in deep subcortical white matter].

We report a case of a brain metastasis of thyroid papillary carcinoma. A 67-year-old man had undergone a radical operation for thyroid papillary carcinoma 6 years before. He had no neurological deficit, but CT showed an enhanced lesion in the left frontal lobe. He underwent gamma knife radiosurgery. Four months later, the lesion with massive peritumoral edema was identified on magnetic resonance imaging (MRI). The edema was treated medically, however, recovery was seen neither on MRI nor clinically. Then left craniotomy was performed, with total resection of the tumor. During the operation Komai's stereotactic instruments were used for CT guided stereotactic surgery. Histopathological analysis of the surgical specimen confirmed mixed necrosis and papillary carcinoma of the thyroid gland. The patient was discharged without neurological deficit and is now kept under observation as an outpatient. Brain metastases from thyroid cancer are rare and we report a case of resection of brain metastasis of a thyroid papillary carcinoma after gamma knife radiosurgery.

Three cases of resected pleomorphic carcinoma.

Pleomorphic carcinoma (PC) is a rare malignancy of the lung. We present 3 cases that were resected. Case 1: The patient was a 75-year-old asymptomatic man whose chest roentgenogram showed a cavity at the right apex. A right upper lobectomy was performed, and the pathological stage was IB (pT2N0M0). After 3 courses of adjuvant chemotherapy, he is alive without relapse 56 months after the operation. Case 2: The patient was a 60-year-old man with left high back pain whose chest roentgenogram showed a mass shadow in the left upper lung field. A left upper lobectomy with partial resection of S6 was performed after induction chemotherapy. The pathological stage was IIIA (pT2N2M0). He died of infection 4 months after the operation during adjuvant chemotherapy. Case 3: A 78-year-old man with hemoptysis underwent aortic arch replacement after a diagnosis of impending rupture of an aortic aneurysm. During the operation, a tumor in the left upper lung lobe was detected. A left upper division segmentectomy was performed one month later. The pathological stage was IIB (pT3N0M0). Despite adjuvant radiotherapy, the patient died of cancer 9 months after the segmentectomy. The final pathological diagnoses for all 3 cases were PC. More cases of PC should be reported to establish optimal management.

Minute localized malignant pleural mesothelioma coexisting with multiple adenocarcinomas.

We report an extremely rare case of minute localized malignant pleural mesothelioma (LMPM) coexisting with multiple lung adenocarcinomas in a 64-year-old woman without a history of smoking or asbestos exposure. A computed tomography scan of the chest displayed total five ground-glass opacities in the lung. Transbronchial lung biopsy from a ground-glass opacity in the posterior segment revealed a bronchioloalveolar carcinoma. With a diagnosis of primary lung cancer, right upper lobectomy and wedge resection of the right lower lobe with systematic lymph node dissection was performed using video-assisted thoracoscopic surgery. Incidentally, a minute gray-white nodule measuring 6 mm was detected on the visceral pleural surface of the right upper lobe. The postoperative histological diagnosis was minute LMPM coexisting with multiple adenocarcinomas.

Primary malignant melanoma of the lung with rapid progression.

This report presents a case of primary malignant melanoma of the lung with rapid progression in a 68-year-old man. During a regular checkup, a chest roentgenogram revealed an abnormal shadow in the left lower lung field. Computed tomography (CT) of the chest revealed an ill-defined tumor shadow measuring 4 x 3 cm in the left upper lobe. A CT-guided lung biopsy suggested a large-cell carcinoma, and left upper lobectomy was performed. Histopathologically, the tumor was comprised of malignant epithelial tumor cells with large amounts of acidophilic cytoplasm and prominent nuclei. A dark brown pigment was observed in the tumor cells. Immunohistochemical staining was positive for S-100 protein and HMB45; staining for cytokeratin, CAM5.2, and chromogranin was negative. The final diagnosis was malignant melanoma of the lung. Two months later, multiple brain metastases developed, and he died of the disease 6 months after the surgery.

Lung adenocarcinomas with micropapillary components.

PURPOSE: Micropapillary adenocarcinoma is becoming increasingly recognized as a prognostically important histological subtype of carcinoma in various organs. This report presents the clinicopathological findings of lung adenocarcinomas with micropapillary components. METHODS: A total of 15 patients with micropapillary components were selected between April 2005 and December 2008. The results of their clinical presentation, metastasis to lymph nodes, pleural invasion, pathological stage, and clinical outcomes were evaluated. RESULTS: In all, 12 patients underwent a lobectomy or bilobectomy with a regional lymph node dissection; 8 showed metastases to the regional lymph nodes at the time of the operation. Altogether, 14 of 15 cases showed lymphovascular invasion; 10 cases were up-staged after the operation because of lymph node metastases or pleural invasion. The duration of follow-up ranged from 1 to 42 months (median 16 months). Seven patients are alive without disease, whereas seven are alive with disease and one patient died of disease. CONCLUSION: These results suggest that the micropapillary components are a manifestation of aggressive behavior, as shown by the frequent lymph node metastases and pleural invasion. Surgeons should search more carefully for metastases and conduct a closer follow-up on these patients when this feature is present with lung adenocarcinoma.

Desmoid tumor of the chest wall in an elderly woman.

We report a case of desmoid tumor of the chest wall in a 79-year-old woman. The patient was referred to our hospital for management of a chest wall mass. Four months previously, the patient noted a small lump in the right lateral chest wall that had rapidly increased in size. Magnetic resonance imaging of the chest revealed a soft tissue tumor in the right lateral chest wall with unclear margins that extended into the intercostal muscles. Positron emission tomography with (18)F-fluorodeoxyglucose (FDG) showed slight FDG accumulation at the lesion. Because open biopsy suggested a desmoid tumor, full-thickness chest wall resection with reconstruction was performed. The final diagnosis was desmoid tumor of the chest wall. Wide surgical resection during the initial operation is an essential element in the treatment of this tumor.

Pulmonary resection for metastases from colorectal carcinoma.

A pulmonary resection of metastatic colorectal carcinoma is an accepted method of treatment. The purpose of this study was to confirm the role of resections for pulmonary metastases from colorectal carcinoma, and to determine the clinical course, outcome, and prognostic factors after surgery. A retrospective analysis was conducted of the records of all patients with pulmonary metastases from colorectal carcinoma who underwent a surgical resection between 1995 and 2008, at a single surgical center. The overall 5-year survival rate was 74%. Multivariate Cox analysis demonstrated that the number of pulmonary metastases (HR: 9.40, 95% confidence interval (CI): 1.08-82.2, P=0.0428) and prethoracotomy carcinoembryonic antigen (CEA) level (HR: 9.79, 95% CI: 1.11-86.8, P=0.0404) were statistically significant predictors of survival after the first pulmonary metastasectomy. In addition, a second resection for recurrent metastases was performed in eight patients, and a third resection was done in one patient. There were no major postoperative complications among the patients who underwent second or third resections. Pulmonary resections are considered to be a safe and effective treatment in selective patients.

Stage Ia malignant pleural mesothelioma: clinical course and appropriate diagnostic process.

Early-stage malignant pleural mesothelioma (MPM) is difficult for physicians to diagnose, and the disease is usually advanced at the time of diagnosis. We report a case of early-stage MPM in a 69-year-old man. The patient presented with fever and left chest pain. A computed tomography scan (CT) of the chest showed a small amount of left pleural effusion and slight left pleural thickening that remained unchanged for 1 year. One month after his inflammatory response spontaneously decreased, follow-up CT of the chest showed reduction in the effusion volume but no change in the pleural thickening. Positron emission tomography with (18)F-fluorodeoxyglucose (FDG) showed increased FDG uptake in the pleural thickening on the left side. Because MPM could not be ruled out, video-assisted thoracoscopic surgery with pleural biopsy was performed for a definitive diagnosis. The postoperative histological diagnosis was early-stage MPM classified as T1a N0M0 disease.