A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component.

Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations.

Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions.

PURPOSE: The diagnosis of gallbladder lesions remains challenging. The efficacy of computed diffusion-weighted imaging (DWI) with high b-values and apparent diffusion coefficient (ADC) for the diagnosis of gallbladder cancer remains unknown. We aimed to investigate the usefulness of computed DWI with high b-values and the combination of computed DWI and ADC in differentiating malignant and benign gallbladder lesions. METHODS: Sixty patients (comprising 30 malignant and 30 benign lesions) who underwent magnetic resonance imaging for gallbladder lesions were included in this retrospective study. Qualitative evaluations were performed using conventional DWI with b1000, computed DWI with b1500, b1000 DWI/ADC, and computed b1500 DWI/ADC, and their diagnostic performances were compared. RESULTS: The sensitivity, specificity, and accuracy of computed b1500 DWI/ADC were 90% (27/30), 80% (24/30), and 85% (51/60), respectively. The accuracy of computed b1500 DWI/ADC was higher than that of conventional b1000 DWI (52%, 31/60, p < 0.001), computed b1500 DWI (72%, 43/60, p = 0.008), and b1000 DWI/ADC (78%, 47/60, p = 0.125). The specificity of computed b1500 DWI/ADC was also higher than that of conventional b1000 DWI (7%, 2/30, p < 0.001), computed b1500 DWI (47%, 14/30, p = 0.002), and b1000 DWI/ADC (67%, 20/30, p = 0.125). No significant difference was observed in the sensitivity between the groups. CONCLUSION: This study shows that computed DWI with high b-values combined with ADC can improve diagnostic performance when differentiating malignant and benign gallbladder lesions. Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions. *Computed DWI with b1500 combined with ADC can improve diagnostic performance when differentiating gallbladder lesions compared with conventional methods (b1000 DWI).

Prognostic Impact of Sarcopenia in Patients With Biliary Tract Cancer Undergoing Chemotherapy.

AIM: Sarcopenia affects the treatment of various cancer types but its impact on chemotherapy efficacy and prognosis in biliary tract cancer remains unclear. Thus, we evaluated whether sarcopenia independently affects the outcome of chemotherapy for biliary tract cancer. PATIENTS AND METHODS: Data of 50 patients who underwent chemotherapy for biliary tract cancer at two affiliated centres were retrospectively analysed. The association of clinical factors, including sarcopenia, with overall survival and time to treatment failure was analysed. RESULTS: Sarcopenia was an independent factor negatively influencing overall survival and time to treatment failure in univariate and multivariate analyses (median overall survival, sarcopenic vs. non-sarcopenic patients: 10.6 vs. 16.6 months; hazard ratio=2.19, p=0.018; time to treatment failure: 5.3 vs. 13.1 months, hazard ratio=2.50, p=0.019). CONCLUSION: Sarcopenia may affect the efficacy of chemotherapy and prognosis in biliary tract cancer. Thus, improving sarcopenia may improve the prognosis of patients with biliary tract cancer undergoing chemotherapy.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Endoscopic features of esophageal adenocarcinoma derived from short-segment versus long-segment Barrett's esophagus.

BACKGROUND AND AIM: The study aims to clarify the endoscopic features and clinicopathological differences in superficial Barret's esophageal adenocarcinoma (s-BEA) derived from short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE). METHODS: We reviewed data of 130 patients (141 lesions) with pathologically confirmed s-BEA (SSBE: 95 patients and 95 lesions; LSBE: 35 patients and 46 lesions). We analyzed endoscopic and clinicopathological features of s-BEA in patients with SSBE and LSBE. RESULTS: The distribution of lesions according to macroscopic findings were as follows (s-BEA in SSBE vs LSBE): flat type (0-IIb), 3.2% (3/95) vs 32.6% (15/46) (P < 0.001); accompanied type 0-IIb, 2.1% (2/95) vs 21.7% (10/46) (P < 0.001); and complex type (0-I + IIb, 0-IIa + IIc, etc.), 30.5% (29/95) vs 50.0% (23/46) (P = 0.025). Complex-type s-BEAs had high incidences of T1b invasions and poorly differentiated components (simple type: 22.5% [20/89] and 18.0% [16/89]; complex type: 59.6% [31/52] and 44.2% [23/52], P < 0.001 and P = 0.002, respectively). In SSBE, 72.6% (69/95) of lesions were located at the right anterior wall (P = 0.01). All flat-type or depressed-type lesions derived from SSBE were identified as reddish areas, whereas only 65.2% (15/23) from LSBE were identified as reddish areas (P < 0.001). CONCLUSIONS: In LSBE, flat-type, accompanied-type 0-IIb, and complex-type lesions were significantly more prevalent. Furthermore, complex-type s-BEAs tended to have T1b invasions and poorly differentiated components. S-BEAs in LSBE should be more carefully evaluated on endoscopic appearance including flat-type and complex-type lesions than in SSBE.

Newly developed magnifying endoscopic classification of the Japan Esophageal Society to identify superficial Barrett's esophagus-related neoplasms.

AIM AND METHODS: The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett's esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy. RESULTS: The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as "visible" or "invisible." Morphologic features were evaluated for "visible" patterns, and were subsequently rated as "regular" or "irregular," and the histology, non-dysplastic or dysplastic, was predicted. CONCLUSION: We introduce the process and outline of the magnifying endoscopic classification.

Treatment Outcomes of Endoscopic Submucosal Dissection for Adenocarcinoma Originating from Long-Segment Barrett's Esophagus versus Short-Segment Barrett's Esophagus.

BACKGROUND: In recent years, effective outcomes of endoscopic submucosal dissection (ESD) for esophagogastric junction cancer including short-segment Barrett's esophagus (SSBE) cancer have been reported. However, the efficacy of ESD for long-segment Barrett's esophagus (LSBE) cancer is unknown. AIM: To clarify the treatment outcomes of ESD for LSBE cancer versus SSBE cancer. METHODS: A total of 86 patients with 91 superficial Barrett's esophageal adenocarcinomas who underwent ESD were enrolled; of these, 68 had underlying SSBE and 18 had LSBE. Procedure outcomes and prognosis were compared. RESULTS: There was no significant difference in age and tumor diameter among patients. The only complication observed was stricture, but it was not significant (2 vs. 9%). No significant difference was observed in the negative horizontal margin rates (94.1 vs. 95.7%), R0 resection rates (83.8 vs. 82.6%), curative resection rates (72.1 vs. 73.9%), and noncurative factors. Both LSBE and SSBE cancer showed favorable 3-year overall survival rates (95.0 vs. 94.4%) in the median observation period of 28.5 months. CONCLUSIONS: ESD for LSBE cancer achieved procedure outcomes and short-term prognosis comparable to SSBE. ESD has the potential to be an effective therapeutic option for esophageal neoplasms in patients with LSBE.

Clinicopathological features of Siewert type II adenocarcinoma: comparison of gastric cardia adenocarcinoma and Barrett's esophageal adenocarcinoma following endoscopic submucosal dissection.

OBJECTIVES: Siewert type II esophagogastric junction adenocarcinoma encompasses both gastric cardia adenocarcinoma (GCA) and Barrett's esophageal adenocarcinoma (BEA) due to short-segment Barrett's esophagus. We compared these two types of Siewert type II esophagogastric junction adenocarcinoma in terms of background factors and clinical outcomes of endoscopic submucosal dissection (ESD). METHODS: We enrolled 139 patients (142 lesions) who underwent ESD from 2006 to 2014 at our institution. Background factors evaluated were age, sex, body mass index, hypertension, hyperlipidemia, hyperuricemia, diabetes mellitus, smoking, drinking, double cancer, and endoscopic findings. Clinical outcomes evaluated were procedure time, en bloc resection rate, curative resection rate, and adverse events. RESULTS: There were 87 GCA lesions (61.2%) and 55 BEA lesions. Features of BEA [55 lesions (38.8%)] included a younger age, small diameter, and a protruding type, along with a high frequency of esophageal hiatal hernia and less mucosal atrophy. There were no significant differences in lifestyle-related background factors between the GCA and BEA groups. Curative resection rate was greater for GCA (81%) than for BEA (66%) (P = 0.01). There were no serious adverse events in either group. Among the factors for noncurative resection, lymphovascular invasion and depth of invasion were greater for BEA (33.3 vs. 7 and 20.7 vs. 8.2%, respectively (P < 0.01). Of the noncured patients, 70% underwent additional surgery and none had postoperative lymph node metastasis. CONCLUSIONS: Siewert type II adenocarcinoma encompasses two types of cancers with different etiologies: GCA and BEA. Although there are no significant differences in lifestyle-related background factors between GCA and BEA, BEA is a risk factor for noncurative resection via ESD.

Surveillance of patients with long-segment Barrett's esophagus: A multicenter prospective cohort study in Japan.

BACKGROUND AND AIM: The incidence of esophageal adenocarcinoma (EAC) in cases with long-segment Barrett's esophagus (BE) has not been investigated in Japan. The aim of this study is to investigate the incidence of EAC in Japanese cases with long-segment BE prospectively. METHODS: This is a multicenter prospective cohort study investigating the incidence rate of EAC in patients with BE with a length of at least 3 cm. Study subjects received index esophagogastroduodenoscopy at the time of enrollment, and they were instructed to undergo yearly follow-up esophagogastroduodenoscopy. Patients in whom EAC was diagnosed in the endoscopic examinations underwent subsequent treatment, and their prognosis was observed. RESULTS: Of 215 enrolled patients, six (2.8%) were initially diagnosed with EAC at the enrollment. Among the remaining 209 patients, 132 received at least one follow-up esophagogastroduodenoscopy. In this follow-up, three EACs developed in 251 observed patient-years (incidence rate: 1.2% per year). Most of the EACs detected at the initial endoscopic examination (5/6, 83%) were already at advanced stages. Meanwhile, all the three lesions detected in the follow-up esophagogastroduodenoscopies were identified as early cancers and subjected to curative resection. CONCLUSIONS: The incidence rate of EAC in Japanese cases with long-segment BE was calculated to be 1.2% in a year.

Accuracy of diagnostic demarcation of undifferentiated-type early gastric cancer for magnifying endoscopy with narrow-band imaging: surgical cases.

BACKGROUND AND AIM: The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) in undifferentiated-type early gastric cancers (UD-type EGCs) is unclear. This study investigated the accuracy of ME-NBI in the diagnostic demarcation. METHODS: Among UD-type EGCs that were initially surgically resected between June 2011 and August 2014 in this hospital, 74 lesions were studied that were preoperatively diagnosed with white-light imaging (WLI) or endoscopic ultrasonography as lesions for which endoscopic treatment was not indicated and found to be early gastric cancers by postoperative pathology. The demarcation line was marked on the most oral and anal sides with argon plasma coagulation using WLI and ME-NBI, and the diagnostic demarcation of cancer was defined as correct, if consistent with the results of postoperative pathology. The length of extension into the proliferative zone, distance between crypts and inflammatory cell infiltration (updated Sydney classification: USC) were compared between the correctly diagnosed and the misdiagnosed cases. RESULTS: The diagnosis was correct in 62 cases (83.8 %). The average distance between crypts in correctly diagnosed and misdiagnosed cases was approximately 1.9 and 1.3 times, respectively, that in normal mucosa (p < 0.0001). The accuracy of diagnosis was higher when atrophy and neutrophil and monocyte infiltration were mild according to the USC (p < 0.05). The additional use of ME-NBI improved the accuracy of diagnosis by 36.5 % compared with the use of WLI alone. CONCLUSION: The use of ME-NBI in the preoperative diagnosis of the demarcation of cancer is useful to prevent postoperative positive surgical margins.

Correlation of the location of superficial Barrett's esophageal adenocarcinoma (s-BEA) with the direction of gastroesophageal reflux.

BACKGROUND: Superficial Barrett's esophageal adenocarcinoma (s-BEA) in Barrett's esophagus frequently occurs in the right wall of the esophagus. Our aim was to examine the correlation between the location of s-BEA and the direction of acid and non-acid reflux in patients with Barrett's esophagus. PATIENTS AND METHODS: We performed 24-h pH monitoring in 33 s-BEA patients using a pH catheter with eight sensors. One sensor was located at the 6 o'clock position in the lower esophagus and sensors 1 - 8 were arranged counterclockwise at the same level. The catheter was positioned at the same level as the s-BEA. We measured the maximal total duration of acid (MTD-A) and non-acid (MTD-NA) reflux. When the direction of MTD-A and MTD-NA coincided with the location of the s-BEA, the case was defined as coincidental and we calculated the rate of coincidence, and the probability of the rate of coincidence was estimated with 95 % confidence intervals (95 %CI). RESULTS: Among the 33 cases of s-BEA examined, the rate of coincidence of both MTD-A and MTD-NA was 24/33 (72.7 %) (95 %CI 0.54 - 0.87). The rate of coincidence of either MTD-A or MTD-NA was 30/33 (90.9 %) (95 %CI 0.76 - 0.98). CONCLUSIONS: Our study revealed that the location of s-BEA mostly corresponds to the direction of MTD-A or MTD-NA. Accurate observation of the distribution of acid or non-acid reflux by pH monitoring would aid early detection of s-BEA by endoscopy.

Accuracy of diagnostic demarcation of undifferentiated-type early gastric cancers for magnifying endoscopy with narrow-band imaging: endoscopic submucosal dissection cases.

BACKGROUND: The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) for undifferentiated-type early gastric cancers (UD-type EGCs) is unclear. The present study examined the accuracy of the diagnostic demarcation of lesions using ME-NBI. METHODS: The study population consisted of 76 patients with UD-type EGC lesions measuring ≤20 mm in diameter using white-light imaging (WLI) and endoscopic ultrasonography and diagnosed as intramucosa and UL(-); all the lesions were confirmed as early gastric cancer based on postoperative pathological examination. All the patients had undergone an initial endoscopic submucosal dissection (ESD) at this hospital between January 2010 and January 2014. After marking with demarcation lines at the utmost oral and anal sites of the lesion using argon plasma coagulation under ME-NBI for intervention, the cases with demarcations that were consistent with the postoperative pathological findings were defined as having been accurately diagnosed. The inflammatory cell infiltration (Updated Sydney System, USS) were also assessed. RESULTS: The diagnostic demarcations of the lesion were consistent in 62 cases (81.6 %). The accurate diagnosis rate was higher for the USS cases with mild neutrophil and monocyte infiltration (P < 0.05). The addition of ME-NBI to WLI improved the accurate diagnosis rate by 27.6 %. CONCLUSION: The use of ME-NBI in diagnostic demarcation of UD-type EGCs is recommended.

Biological behavior of the intramucosal Helicobacter pylori-negative undifferentiated-type early gastric cancer: comparison with Helicobacter pylori-positive early gastric cancer.

BACKGROUND: The differences in the growth morphology, proliferative ability, and background mucosa of the cancer between Helicobacter pylori (HP)-positive (HP+) gastric cancer (GC) and HP-negative (HP-) GC are still unclear. To clarify the differences, we compared the characteristics of the two types of cancer. METHODS: Of the 91 patients with undifferentiated-type early GC who underwent endoscopic treatment at our hospital between August 2005 and April 2011, 23 HP- GC patients (all of whom had signet ring cell carcinoma measuring 20 mm or less in diameter) and 46 HP+ GC patients with signet ring cell carcinoma measuring 20 mm or less in diameter (out of a total of 68 HP+ GC patients) were enrolled in this study. Endoscopic atrophy and background mucosa were classified according to the updated Sydney system. The proliferative capacity of the cancer was assessed by examining the MIB-1 labeling index. RESULTS: With regard to the growth in the mucosal layer, the proportion of patients with cancer confined to the proliferative zone was significantly higher in the HP- GC group. Moderate or severer atrophy, intestinal metaplasia, mononuclear cell infiltration, and neutrophil infiltration according to the updated Sydney system were significantly commoner in the HP+ GC patients. Also, the MIB-1 labeling index was significantly higher in the HP+ GC group. CONCLUSION: HP+ GC appeared to show a higher proliferative capacity, more extensive spread, and more rapid progression, and inflammation associated with HP infection was suggested to be involved in the proliferation of this type of GC.

[Endoscopic therapy for cancer of the esophagogastric junction].

In Japan, the criteria for cancer of the esophagogastric junction (EGJ) are that the center of the lesions are located within 2cm from the EGJ orally and anally. The main histology of these lesions are squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma of the esophagus is treated following the guidelines published by the Japan Esophageal Society. This paper focuses on EGJ adenocarcinomas, which include cardiac gastric cancer and Barrett's cancer originating from the short-segment Barrett's esophagus. EGJ cancer is resected endoscopically at the termination of the palisade vessels or upper end of the gastric fold. The various types of cancer involving the EGJ are treated following the guidelines published by each medical specialist society in Japan. The main endoscopic treatment is endoscopic submucosal dissection. The EGJ is a narrow space, and therefore lesions are approached from the oral approach or anal approach using a reverse endoscope. Bleeding, perforation, and stenosis are major complications. When two-thirds or more of the wall is resected, stenosis occurs. Endoscopic therapy for cancer originating in the EGJ has not yet been fully established.

Magnifying endoscopy with narrow-band imaging findings in the diagnosis of Barrett's esophageal adenocarcinoma spreading below squamous epithelium.

It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 µm from the surface and disappeared at a depth of approximately 300 µm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 µm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.

Extensive 0-IIc (undifferentiated carcinoma) lesion around a gastric adenoma: a case report.

A 73-year-old woman underwent esophagogastroduodenoscopy (EGD) at a local hospital, which revealed a flat elevated lesion, approximately 15 mm in diameter, in the posterior wall of the lower gastric body. At our hospital, a repeat EGD and biopsy led to a diagnosis of moderately dysplastic adenoma. The patient requested endoscopic submucosal dissection (ESD). Histopathology revealed a gastric adenoma with negativity for tumor at the vertical margin; however, the horizontal margin was positive for cancer with an undifferentiated carcinoma surrounding the adenoma. EGD was repeated, and a discolored area was found around the ESD scar. Biopsy revealed an undifferentiated carcinoma. Laparoscopic distal gastrectomy was performed, and postoperative histopathology also revealed an undifferentiated carcinoma (50 mm in diameter) surrounding the ESD scar; this lesion was an undifferentiated adenocarcinoma that was colocalized with and spread out to surround the original adenoma. This case is important for consideration of the pattern of development and progression of superficial spreading gastric cancer.

Spontaneous regression of hepatocellular carcinoma repeated 3 times with invasion of portal vein and inferior vena cava: report on a rare case.

A 65-year-old man suffered from advanced hepatocellular carcinoma in the right lobe of the liver, for which he received no treatment. His serum was positive for hepatitis C antibody. In spite of his poor prognosis, he remained in good clinical condition and at 6-month follow-up the tumor had regressed without specific treatment, as assessed both radiologically and from a decrease of a previously elevated serum tumor marker level (1st regression). The tumor regrew in size, but at 23-month follow-up could no longer be visualized radiologically (2nd regression). A follow-up computed tomography (CT) scan did not show any relapse of hepatocellular carcinoma until March 2005. At that time, a new lesion had developed in the caudate lobe and tumor size had increased to ≥10 cm in diameter, and in June 2006 had invaded the portal vein and inferior vena cava. Afterwards, the tumor lesion gradually decreased again. In June 2007, a CT scan showed a further reduction of tumor size (3rd regression). Here, we report a rare case of spontaneous regression of hepatocellular carcinoma in which spontaneous regression and recurrence were repeated 3 times.