In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.

Securing an appropriate proximal resection margin (PRM) is crucial for oncological safety in treating gastric cancer. This study investigated the clinicopathological characteristics of patients with incomplete PRM length of <2 cm in early gastric cancer. Clinicopathological data of 1,493 patients who underwent subtotal gastrectomy for early gastric cancer in 2012 to 2021 were retrospectively reviewed. Patients were divided into the PRM length of <2 cm and ≥2 cm groups based on pathological results. Univariate and multivariate analyses evaluated factors for incomplete PRM length. Factors related to patients with a relative PRM positive were also analyzed. The proportion of patients with a PRM length of <2 cm was 17.9% (267/1,493). Multivariate regression analysis revealed that age <50, preoperative endoscopic size of ≥3 cm, size discrepancy of ≥2 cm, and midbody tumor with a lesser curvature significantly contributed to the PRM length of <2 cm. Twenty-four patients had a relative PRM positive (24/1493, 1.6%). An incomplete PRM was the only risk factor for a positive relative PRM. Surgical treatment for early gastric cancer requires an accurate preoperative endoscopic tumor size and location evaluation. A more aggressive resection is recommended for patients with age <50, preoperative endoscopic size of ≥3 cm, size discrepancy of ≥2 cm, and midbody tumor with a lesser curvature.

Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy.

We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as "neoplasia," "negative for neoplasia," or "indefinite for neoplasia," and the frozen section diagnosis was compared with the final pathological results of the ESD specimens.

Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen's kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837-0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD.

Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD.

Endoscopic submucosal dissection (ESD) is an effective method for resecting gastric adenomas and adenocarcinomas. A significant discrepancy was observed between endoscopic and pathological sizes in samples obtained from patients undergoing ESD. This study elucidates the factors affecting size discrepancy after formalin fixation.

The records of 64 patients with 69 lesions were analyzed, including 50 adenomas and 19 adenocarcinomas. Data on location, gross shape, histology, and size after fixation in formalin were collected.

The mean size of the resected specimen appeared to decrease after formalin fixation (37.5 mm prefixation vs. 35.8 mm postfixation, p<0.05). The mean long axis diameter of the lesions was 20.3±7.9 mm prefixation and 13.4±7.9 mm postfixation. Size differences in lesions smaller than 20 mm were significantly greater than those in lesions larger than 20 mm (7.6±5.6 mm vs. 2.5±5.8 mm, p<0.01). In multivariate analysis, a tumor size of ≥20 mm was found to be an independent factor affecting size postformalin fixation (p<0.05).

The endoscopic size of lesions before ESD may be underestimated in tumors larger than 20 mm in size. Therefore, increased attention must be paid during ESD to avoid instances of incomplete resection.

The histologic evaluation of biopsy samples collected from the surrounding mucosa has conventionally been used to determine the horizontal extent of early gastric cancer. Recently, optical delineation using magnifying image-enhanced endoscopy (IEE) has been considered an alternative method to histologic evaluation. This study aimed to assess the clinical outcome and efficacy of this method in identifying cancer margins.

Overall, 921 patients with 1018 differentiated-type early gastric tumors who underwent endoscopic submucosal dissection (ESD) were examined. Before ESD, the lesions were classified based on whether they have clear or unclear margins on magnifying IEE. When the lesions had clear margins, the marking dots were placed outside the margins without a negative biopsy. Successful delineation was defined as lesions with clear margins and accurate delineation based on histopathological examination. The primary outcome was the accuracy of optical delineation without a negative biopsy compared with histopathological diagnosis. Moreover, the clinicopathological factors associated with an unsuccessful delineation were assessed.

Of 1018 lesions, 820 had a clear margin and 198 an unclear margin. Of 820 lesions with a clear margin, 817 and 3 had an accurate and inaccurate delineation, respectively, according to the histological examination. Accordingly, the accuracy rate of optical delineation was 99.6% (817/820). The significant independent factors associated with an unsuccessful delineation were absence of Helicobacter pylori infection after eradication, tumor size > 20 mm, and moderate differentiation.

Optical delineation may be an alternative method to histological evaluation in lesions with a clear margin on magnifying IEE.

For successful treatment of early gastric cancers (EGCs), it is crucial to define the horizontal border of the lesion with high accuracy. Acetic acid-indigo carmine (AI) chromoendoscopy has been used to determine the horizontal border in EGCs, but this technique is less potent in certain situations. Mucin phenotype in gastric cancers refers to biological differences in precursor lesions and differences in histopathologic findings, and it might affect AI chromoendoscopy findings. We aimed to investigate the association between mucin phenotype and AI chromoendoscopy findings in EGCs.

We prospectively evaluated 126 lesions in 126 patients with endoscopically diagnosed EGCs. Conventional endoscopy and AI chromoendoscopy findings of these lesions before treatment were prospectively analyzed. The border distinction between the lesion and surrounding mucosa was classified as distinct or indistinct on conventional endoscopy and AI chromoendoscopy, respectively. Mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null type by immunohistochemistry.

The lesion borders were distinct in 46.8% (59/126) of the lesions assessed using conventional endoscopy and in 73.0% (92/126) of those assessed with AI chromoendoscopy (p < 0.001). The border distinction rate of differentiated-type cancers on AI chromoendoscopy was significantly higher than that on conventional endoscopy (66/71 [93.0%] vs. 34/71 [47.9%], p < 0.001), but the border distinction rate of undifferentiated-type cancers on AI chromoendoscopy was not different from that on conventional endoscopy (26/55 [47.3%] vs. 25/55 [45.5%], p = 0.848). Compared with conventional endoscopy, AI chromoendoscopy identified borders in a significantly higher percentage of gastric, intestinal, and gastrointestinal mucin types; however, there was no difference in AI chromoendoscopy findings according to the mucin phenotype (p = 0.271).

AI chromoendoscopy was effective in horizontal border delineation in differentiated-type EGCs, but not in undifferentiated-type EGCs. Mucin phenotype had no effect on border distinction using AI chromoendoscopy.

Gastric intestinal-type adenocarcinoma with anastomosing glands (IAAG) is characterized by architectural abnormality with frequent anastomosing glands and low-grade cytologic atypia. Clinicopathologic features and long-term outcomes of endoscopic submucosal dissection (ESD) for IAAG remain unclear.

This study included 2828 patients who underwent ESD for early gastric cancers (EGCs) (78 IAAGs [2.6%] and 2893 well-differentiated [WD] or moderately differentiated [MD] EGCs [97.4%]). Clinicopathologic features and short-term and long-term outcomes of ESD for IAAG were reviewed and compared with those for WD or MD EGCs.

Gastric IAAGs were larger and more likely to be confined to the lamina propria than WD or MD EGCs. Histological heterogeneity, flat or depressed lesion and lateral resection margin (LRM) involvement were observed with significantly higher frequencies in IAAGs than in WD or MD EGCs. En bloc with R0 resection and curative resection rates of IAAGs were 79.5% and 73.1%, respectively, and both were significantly lower than those of WD or MD EGCs (93.8% and 82.9%). LRM involvement accounted for 57.1% of the non-curative resection cases in gastric IAAGs. Half of IAAGs with LRM involvement had a crawling pattern at tumor periphery. Among patients undergoing curative ESD for IAAG, no recurrences occurred during a median 52 months of follow-up. No lymph node metastasis was found in any of IAAG patients undergoing additional surgery after ESD.

Gastric IAAGs have distinct clinicopathologic features from WD or MD EGCs. Given the favorable long-term outcomes after curative resection, ESD can be indicated for early gastric IAAGs.

Endoscopic submucosal dissection (ESD) is widely accepted for treating early gastric cancer (EGC); however, there can be cases of incomplete resection due to not only technical problems, but also misdiagnosis. Our aim was to identify factors associated with incomplete gastric ESD due to misdiagnosis.

A total of 2,268 patients with solitary EGCs at initial onset underwent ESD with curative intent at our hospital from 1999 to 2008. We retrospectively assessed the clinicopathological factors by comparing the two groups of incomplete ESD cases due to misdiagnosis (cases with a positive lateral margins [LM] [Group A] or those with a positive vertical margins [VM] [Group B]) with complete ESD cases using multivariable analysis.

Complete ESD was achieved in 2,097 patients. The 171 patients with incomplete ESDs were divided into 109 with a positive LM and 80 with a positive VM (overlapped). Except 49 cases with a positive LM due to technical problems, a positive LM due to misdiagnosis was identified in 60 cases (Group A). Excluding 32 cases with a positive VM due to technical problems, a positive VM due to misdiagnosis was found in 48 cases (Group B). Significant independent factors (odds ratios [OR]; 95 % confidence intervals [CI]) for each group were as follows: Group A: size > 20 mm (5.4; 3.0 - 9.9), undifferentiated-type (4.1; 1.8 - 9.0), submucosal invasion (2.0; 1.1 - 3.4) and location of upper/middle (1.9; 1.0 - 3.6); Group B: size > 20 mm (3.0; 1.6 - 5.5), undifferentiated-type (3.0; 1.1 - 8.0) and location of upper/middle (2.4; 1.2 - 4.8).

Endoscopists must be aware of these factors associated with incomplete gastric ESD due to misdiagnosis to further decrease their incidence.

Although magnifying endoscopy with narrow-band imaging (ME-NBI) is reported to be useful for delineating the horizontal extent of early gastric cancers (EGCs), there are few reports which have objectively demonstrated the superiority of ME-NBI over chromoendoscopy with indigo carmine for this purpose. We conducted an exploratory comparison of the diagnostic accuracy of both modalities for the delineation of EGCs using prospectively collected data, and clarified the clinicopathological features related to inaccurate evaluation of the horizontal extent of EGCs.

EGCs were assigned to the oral narrow-band imaging (O-NBI) group or the oral chromoendoscopy (O-CE) group before endoscopic submucosal dissection (ESD). The oral border was observed according to assignment, and the anal border with the other modality. The horizontal extent of the tumor was evaluated by each modality and a marking dot was placed on the visible delineation line. After ESD, the marking dots were identified pathologically and defined as "accurate evaluation" if they were located within 1 mm of the pathological tumor border. We compared the rate of accurate evaluation of ME-NBI and chromoendoscopy, and analyzed the clinicopathological features related to inaccurate evaluation.

A total of 113 marking dots evaluated by ME-NBI and 116 evaluated by chromoendoscopy were analyzed. The rate of accurate evaluation by ME-NBI was significantly higher than that by chromoendoscopy (89.4 % vs 75.9 %, P = 0.0071). The EGCs with flat borders and large EGCs were significantly related to inaccurate evaluation using ME-NBI. There were no significant factors related to inaccurate evaluation with chromoendoscopy.

The accurate evaluation rate of the horizontal extent of EGCs by ME-NBI is significantly higher than that by chromoendoscopy.

UMIN000007641.

Discrepancies in the clinicopathologic parameters pre- and post-endoscopic submucosal dissection (ESD) sometimes necessitate additional surgical resection. The aim of this study was to assess such discrepancies in clinicopathologic parameters before and after ESD in the context of reducing the risk of failure of curative ESD.

Data on 712 early gastric cancer patients were prospectively collected from 12 university hospitals nationwide. The inclusion criteria were differentiated carcinoma <3 cm in size, no ulceration, submucosal invasion <500 μm, and no metastasis. Clinicopathologic factors were compared retrospectively.

The discrepancy rate was 20.1 % (148/737) and the most common cause of discrepancy was tumor size (64 cases, 8.7 %). Ulceration, undifferentiated histology, and SM2 invasion were found in 34 (4.6 %), 18 (2.4 %), and 51 cases (6.9 %), respectively. Lymphovascular invasion (LVI) was observed in 34 cases (4.6 %). Cases with lesions exceeding 3 cm in size showed more frequent submucosal invasion, an elevated gross morphology, and upper and middle locations (p < 0.05). In the cases with ulceration, depth of invasion (DOI) was deeper than in the cases without ulceration (p = 0.005). Differentiation was correlated with DOI and LVI (p = 0.021 and 0.007). DOI was correlated with tumor size, ulceration, differentiation, LVI, gross type, and location. There were statistically significant differences between mucosal cancer cases and submucosal cancer cases in tumor size, differentiation, ulceration, LVI, and location.

The overall discrepancy rate was 20.1 %. To reduce this rate, it is necessary to evaluate the DOI very cautiously, because it is correlated with other parameters. In particular, careful checking for SM-invasive cancer is required due to the high incidence of LVI irrespective of the depth of submucosal invasion.

There are often discrepancies between the pretreatment evaluation of gastric neoplasms by endoscopy with biopsy and the final diagnosis of resected specimen in terms of pathology and depth of invasion. We evaluated the spectrum of discrepancies between pretreatment and posttreatment diagnosis which may deliver significant differences on clinical practice.

A total of 2041 patients with gastric dysplasia or cancer who underwent curative endoscopic resections or surgeries in 2012 were enrolled. Patients were classified into five different diagnostic groups: low-grade dysplasia (LGD), high-grade dysplasia (HGD), absolute indication early gastric cancer (AI-EGC), beyond absolute indication early gastric cancer (BAI-EGC), and advanced gastric cancer (AGC). The choice of initial treatment and final pathologic diagnosis was analyzed.

The study patients belonged to the following pretreatment diagnostic groups: LGDs in 162, HGDs in 164, AI-EGCs in 396, BAI-EGCs in 824, and AGCs in 495 cases. Posttreatment diagnostic groups were LGDs in 140, HGDs in 121, AI-EGCs in 322, BAI-EGCs in 947, AGCs in 505, and no residual tumor in 6 cases. In general, 6.9 % (141/2041) of cases were downgraded and 15.9 % (324/2041) were upgraded. Thirty-four percent of pretreatment HGDs (56/164) were changed to cancers after endoscopic resection. Thirty-three percent of pretreatment AI-EGCs (131/396) were regrouped as posttreatment BAI-EGCs. The additional surgery rate in each pretreatment group was 0.6 % in LGD, 4.3 % in HGD, 15.7 % in AI-EGC, 23.6 % in BAI-EGC among the patients with initial endoscopic resection (p < 0.01).

Twenty-three percent of gastric neoplasms changed in their final diagnostic group after endoscopic resection or surgery. This discrepancy should be considered when the initial treatment strategy is being selected.

Although endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), there is no consensus regarding the management of positive horizontal margin (HM) despite en bloc ESD. The aim of the current study was to identify the risk factors and optimal management of positive HM in EGCs resected by en bloc ESD.

A total of 890 consecutive patients with 1,053 intramucosal EGCs resected by en bloc ESD between April 2005 and June 2011. Clinicopathological data were retrieved retrospectively to assess the positive HM rate, local recurrence rate, risk factors for positive HM, and outcomes of treatment for local recurrent tumor. Positive HM was defined as a margin with direct tumor invasion (type A), the presence of cancerous cells on either end of 2-mm-thick cut sections (type B), or an unclear tumor margin resulting from crush or burn damage (type C).

The positive HM rate was 2.0% (21/1,053). The local recurrence rate was 0.3% (3/1,053). All local recurrent tumors were intramucosal carcinomas, and were resected curatively by re-ESD. Multivariate analysis with logistic regression showed tumor location in the upper third of the stomach and lesions not matching the absolute indication to be independent risk factors for positive HM.

The risk factors for HM positivity in cases of EGC resected by en bloc ESD are tumor location in the upper third of the stomach and dissatisfaction of the absolute indication for curative ESD.