[Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases].

OBJECTIVE: To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis. METHODS: A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively. RESULTS: 23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001). CONCLUSION: Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.

Rate of Incidental Pathological Lesions in Reduction Mammoplasty Specimens and Incidence of Invasive Breast Carcinoma Following Breast Reduction Operation.

INTRODUCTION: Reduction mammoplasty (RM) is one of the most frequently performed surgical procedures. The incidental determination of significant pathologic lesions (SPL), that is precursor and malignant lesions, in RM specimens is rare. The aim of this study was to determine the frequency of SPL in RM specimens, to evaluate the relationship between SPL and clinicopathological factors, and to examine the incidence of invasive breast carcinoma forming in the remaining breast tissue during the postoperative follow-up period developing in patients after RM operation. MATERIAL AND METHOD: This retrospective study included 874 females who underwent RM operation between January 2012 and January 2021. Demographic, clinicopathological findings, and preoperative radiological findings were recorded. The patients were followed up after the RM operation in respect of the first occurrence of breast cancer. RESULTS: Invasive carcinoma was determined in 0.2% and SPL in 3.5% in RM. The probability of SPL determination was greater in patients aged ≥ 40 years and with ≥ 4 paraffin blocks (p=0.038, p=0.01, respectively). No statistically significant difference was found between patients with and without SPL in respect of radiological findings (p=0.35). The mean postoperative follow-up period was 53.6 months, and invasive carcinoma was diagnosed during follow-up in 0.2% of all patients (6.9% of the patients with SPL). CONCLUSION: Age over 40 years and an increased number of sampled blocks were found to be factors increasing the possibility of the determination of precursor and malignant lesions in RM specimens. RM could decrease the risk of the development of breast cancer. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dysplasia and carcinoma of the gallbladder: pathological evaluation, sampling, differential diagnosis and clinical implications.

Pathological evaluation of gallbladder neoplasia remains a challenge. A significant proportion of cases presents as clinically and grossly inapparent lesions, and grossing protocols are not well established. Among epithelial alterations, pseudo-pyloric gland metaplasia is ubiquitous and of no apparent consequence, whereas goblet cell metaplasia and a foveolar change in surface cells require closer attention. Low-grade dysplasia is difficult to objectively define and appears to be clinically inconsequential by itself; however, extra sampling is required to exclude the possibility of accompanying more significant lesions. For high-grade dysplasia ('high-grade BilIN', also known as 'carcinoma in situ'), a complete sampling is necessary to rule out invasion. Designating in-situ or minimally invasive carcinomas limited to muscularis or above as early gallbladder carcinoma (EGBC) helps to alleviate the major geographical differences (West/East) in the criteria for 'invasiveness' to assign a case to pTis or pT1. Total sampling is crucial in proper diagnosis of such cases. A subset of invasive GBCs (5-10%) arise from the intracholecystic neoplasm (ICN, 'adenoma-carcinoma sequence') category. Approximately two-thirds of ICNs have invasive carcinoma. However, this propensity differs by subtype. True 'pyloric gland adenomas' (> 1 cm) are uncommon and scarcely associated with invasive carcinoma. A distinct subtype of ICN composed of tubular, non-mucinous MUC6+ glands [intracholecystic tubular non-mucinous neoplasm (ICTN)] forms a localised pedunculated polyp. Although it is morphologically complex and high-grade, it appears to be invasion-resistant. Some of the invasive carcinoma types in the gallbladder have been better characterised recently with adenosquamous, neuroendocrine, poorly cohesive and mucinous carcinomas often being more advanced and aggressive.

Evaluation of pathology and environmental variables contributing to hepatopancreatic necrosis syndrome of Chinese mitten crab, Eriocheir sinensis.

Hepatopancreatic Necrosis Syndrome (HPNS) severely impacts the Chinese mitten crab (Eriocheir sinensis) industry. However, little knowledge of the aetiology and pathogenesis of the disease causes significant difficulties in its prevention and control. In this study, we conducted a pathological analysis of HPNS through time-integrated large-volume sampling, to clarify the disease characteristics and mechanism of HPNS-afflicted crabs; besides, animal models were constructed to verify the pathological diagnosis. The results showed that the hepatopancreas was the principal target organ of HPNS; multiple correspondence analysis revealed that the main histopathological characteristics included non-interstitial atrophic hepatopathy diseases such as hepatic tubule atrophy, dilated hepatic tubules, and hepatic tubule necrosis. Additionally, the muscles also showed signs of disease, including myofibre atrophy, necrosis, and inflammation. Ultrastructural studies showed prominent apoptosis and autophagy-like alterations in the hepatopancreas of HPNS-afflicted crabs. Further, the establishment of animal models revealed that the double variate stimulation of environmental variables such as abamectin/sewage with nutrition deficiency could result in HPNS-similar lesions. Based on these studies, we concluded that HPNS is a chronic hepatopancreas-initiated energy-consumed disease with a low likelihood of pathogen but a high probability of environment and nutrition.

The rate of incidental atypical and malignant breast lesions in reduction mammoplasty specimens.

AIMS: Reduction mammoplasty (RM) is one of the most common plastic surgeries in the United States. We aimed to demonstrate the rate of incidental atypical and malignant breast lesions (AMBL) found in RM specimens and the impact of the number of submitted tissue sections on the rate of AMBL. METHODS AND RESULTS: We analysed our database for patients who had undergone reduction mammoplasty between 2000 and 2018. Patients with a history of breast cancer were excluded from the study. All pathology reports were analysed for AMBL (ALH, LCIS, FEA, ADH, DCIS, invasive carcinoma). The grossing protocol was to submit 10 sections from each breast between 2000 and 2013 and six sections between 2014 and 2018. One hundred and sixty-nine of 5208 patients (3.3%) and 216 of 10 340 RM specimens (2.1%) showed at least one AMBL. Nineteen (0.36%) patients had incidental cancer. The median age of patients with AMBL was significantly higher than patients without ABL (aged 59 years versus 45 years). There was no cancer in patients aged <30 years. The age-controlled rate of overall AMBL as well as atypia and cancer only did not decrease by submitting fewer sections during the 2014-18 period compared to the 2010-13 period. CONCLUSIONS: Decreasing the number of tissue sections from 10 to six did not lead to a significant decrease in the rate of overall AMBL or cancer. Our data suggest that submitting six tissue sections from each breast for patients aged >30 years and two sections from each breast for patients aged <30 years would be sufficient.

A novel evaluation method for determining drug-induced hepatotoxicity using 3D bio-printed human liver tissue.

Predicting drug-induced liver injury is important in early stage drug discovery; however, an accurate prediction with existing hepatotoxicity evaluation tools is difficult. Conventional monolayer (2D) cultures have short viabilities and are therefore inappropriate for performing long-term toxicity tests. Conventionally used 200-µm spheroids also have toxicity detection limits. The goal of this study was to develop a humanized liver tissue capable of evaluating long-term toxicity with high sensitivity. Spheroids consisting of co-cultured cryopreserved primary human hepatocytes and human hepatic stellate cells were developed using a 3D bio-printer. The "3D bio-printed liver tissue", of ∼1 mm, was then used for long-term viability assessments (over 25 days) based on ATP, albumin, and urea levels. Hepatotoxicity evaluation was performed by analyzing the expression of genes involved in drug metabolism and transport over a 2-week drug exposure period. The 3D bio-printed liver tissue showed improved viability and enhanced gene expression of enzymes related to drug metabolism and transport, as compared to the controls. Additionally, the 3D bio-printed liver tissue demonstrated a high sensitivity for hepatotoxicity evaluation when combined with pathological evaluation and measurements for ATP production, and secretion of albumin and urea. In conclusion, the 3D bio-printed liver tissue was able to detect the toxicity of compounds that was, otherwise, undetected by 2D culture and conventionally used spheroids. These findings demonstrate a 3D bio-printed liver tissue with increased accuracy of hepatotoxicity prediction in the early stages of drug discovery, as compared to currently available methods.

Association between pathologic features of peripheral nerves and postoperative anal function after neoadjuvant therapy for low rectal cancer.

PURPOSE: Neoadjuvant chemoradiotherapy (CRT) for rectal cancer improves local control but also induces severe postoperative anal dysfunction that may be related to neural degeneration. The aims of the study were to identify pathological features of neural degeneration caused by neoadjuvant CRT or neoadjuvant chemotherapy (NAC) and to evaluate the association between neural degeneration and anal function. METHODS: A retrospective study using chronologically different groups was performed in 95 patients with rectal cancer treated with curative resection with neoadjuvant CRT (n = 47), NAC (n = 27), or surgery alone (no neoadjuvant therapy) (n = 21) at National Cancer Center Hospital East from 2001 to 2014. Peripheral nerve degeneration was evaluated histopathologically using H&E stained sections, based on karyopyknosis, vacuolar or acidophilic degeneration, denucleation, adventitial neuron change, and fibrosis. Morphological analysis of peripheral nerves was compared among the three groups. The association between pathological features and anal function (Wexner Score) was evaluated. RESULTS: After CRT, the degree of fibrosis around the tumor was severe, and neural degeneration was found in peripheral neurons. With NAC and surgery alone, there was little fibrosis and neural degeneration. Pathological changes after CRT were more pronounced than those after NAC, indicating greater tissue degeneration due to CRT. There was an association between anal function and degeneration score in the CRT group, but not in the other groups. CONCLUSIONS: Peripheral nerves in patients who received neoadjuvant CRT showed characteristic pathological features indicating greater degeneration, compared with patients who received NAC. Neural degeneration is associated with anal function and several pathological factors after CRT.

Comparison of the pathological response of the mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery and long-course chemoradiotherapy in patients with rectal cancer.

BACKGROUND: The aim of this study was to compare the pathological response of mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery (SCRT-delay) and long-course chemoradiotherapy (LC-CRT) in patients with rectal cancer. METHOD: The resected primary tumor specimens following the two different approaches were assessed utilizing the tumor regression grade (TRG 0-4), and each positive lymph node was assessed according to the lymph node regression grade (LRG 1-3), with TRG 4 and LRG 3 indicating total regression. The lymph node sizes were measured to elucidate any correlation with LRG scores. RESULTS: Seventy-four patients with ypN-positive rectal cancer had 220 positive lymph nodes following the SCRT-delay, and 48 patients had 141 positive lymph nodes following the LC-CRT. The distribution of LRG 1/2/3 in the two groups was 123/72/25 and 60/31/50 (p < 0.001), respectively, and the distribution of TRG 0/1/2/3/4 in the two groups was 36/19/19/0 and 12/15/20/1 (p = 0.005), respectively. The requirements of total regression of positive lymph nodes were a primary tumor degenerated to TRG 3 with a size less than 6 mm in SCRT-delay (sensitivity, 60.9 %) or a primary tumor degenerated to TRG 2-4 with a size less than 5 mm at TRG 2 (sensitivity, 57.6 %) or 6 mm at TRG 3 and 4 (sensitivity, 84.2 %) in LC-CRT as indicated by the receiver operating characteristic curve analysis. CONCLUSION: The tumor regression effect of LC-CRT on the primary tumor and positive nodes was more favorable than SCRT-delay, and LC-CRT is able to predict the LRG 3 response with a high sensitivity.

Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

INTRODUCTION: Lymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. METHODS: Retrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). RESULTS: A total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN - group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN - patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). CONCLUSION: Conventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery.

OBJECTIVE: To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery. METHODS: Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: The 124 enrolled patients had a median age of 62 years (range, 35-79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR]=1.94, p=0.003), residual cancer at the end of surgery ≥1cm (HR=3.78, p<0.001), and histological grade 0-1 (HR=1.65, p=0.03) were independent predictors of decreased OS. Grade 0-1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio=8.42, p=0.003). CONCLUSIONS: Residual disease of ≥1cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.

Histopathological findings affect quantitative values of single photon emission computed tomography in patients with antiresorptive agent-related osteonecrosis of the jaws.

Objectives: This study investigated the relationships between quantitative values calculated from bone single photon emission computed tomography/computed tomography (SPECT/CT) images and histopathological findings observed in surgical specimens from patients with antiresorptive agent-related osteonecrosis of the jaw (ARONJ); it sought to clarify histopathological factors that cause accumulation in bone SPECT/CT images of patients with ARONJ. Methods: This study included 81 pathological specimens of 21 lesions obtained from 18 patients with ARONJ who underwent SPECT/CT and jaw resection. The maximum standardized uptake value (SUVmax) of each volume of interest of the specimens was calculated using RAVAT® software. The ratio of the SUVmax to the mean value of SUVmax in temporal bone was termed rSUVmax. The rSUVmax and pathological findings (sequestration, degree of fibrosis, degree of trabecular bone destruction, degree of inflammatory cell infiltration, and vascularity) were compared using the Mann-Whitney U test and the Kruskal-Wallis test. Results: In univariate analysis with rSUVmax as the dependent variable, the pathological findings of sequestration (P=0.058), degree of fibrosis (P=0.810), degree of trabecular bone destruction (P=0.237), degree of inflammatory cell infiltration (P=0.120), and vascularity (P=0.111) showed no significant difference among the groups for each variable. Conclusions: We found no association between quantitative values in bone SPECT/CT and histological changes in ARONJ, probably because bone SPECT/CT has limited spatial resolution. Limitations of this study may include the imaging findings of a decrease in tracer accumulation because of an involucrum of necrosed bone, various histopathological findings in ARONJ, and failure to consider the effect of preoperative anti-inflammatory treatment.

Automated recognition of glomerular lesions in the kidneys of mice by using deep learning.

Background: In recent years, digital pathology has been rapidly developing and applied throughout the world. Especially in clinical settings, it has been utilized in a variety of situations, including automated cancer diagnosis. Conversely, in non-clinical research, it has not yet been utilized as much as in clinical settings. We have been performing automated recognition of various pathological animal tissues and quantitative analysis of pathological findings, including liver and lung. In this study, we attempted to construct an artificial intelligence (AI)-based trained model that can automatedly recognize glomerular lesions in mouse kidneys that are characterized by complex structures. Materials and methods: By using hematoxylin and eosin (HE)-stained whole slide images (WSI) from Col4a3 KO mice as variation data, normal glomeruli and glomerular lesions were annotated, and deep learning (DL) was performed with the use of the neural network classifier DenseNet system in HALO AI. The trained model was refined by correcting the annotation of misrecognized tissue area and reperforming DL. The accuracy of the trained model was confirmed by comparing the AI-obtained results with the pathological grades evaluated by pathologists. The generality of the trained model was also confirmed by analyzing the WSI of adriamycin (ADR)-induced nephropathy mice, which is a different disease model. Results: Glomerular lesions (including mesangial proliferation, crescent formation, and sclerosis) observed in Col4a3 KO mice and ADR mice were detected by our trained model. The number of glomerular lesions detected by our trained model were also highly correlated with that of counted by pathologists. Conclusion: In this study, we constructed a trained model allowing us to automatedly recognize glomerular lesions in the mouse kidney with the use of the HALO AI system. The findings and insights of this study will facilitate the development of digital pathology in non-clinical research and improve the probability of success in drug discovery research.

Pathological evaluation 18 years after bare-metal stent implantation in the superficial femoral artery.

Bare-metal stents (BMSs) have been generally applied for the treatment of peripheral artery disease in patients with femoropopliteal disease. However, very long-term pathological findings after BMS implantation have not been elucidated to date. We experienced an autopsy case in which we performed a pathological evaluation 18 years after BMS implantation in the right superficial femoral artery. The BMS was totally occluded and filled with remarkable neointima formation. Neointima was mainly composed of a lot of rather atrophic smooth muscles and intercellular spaces containing dense collagenous fibers. Furthermore, regional fatty infiltration was also observed, but inflammatory cell infiltration, such as macrophages and lymphocytes, was not recognized obviously even around the struts. Judging from the pathological findings, the main mechanism of the very long-term in-stent restenosis in the patients with femoropopliteal disease was continuous proliferation of smooth muscle cells that led to the totally occlusive disease. This observation leads us to speculate that continuous elution of an anti-proliferating drug over a longer duration, at least beyond 1 year, would be effective to prevent chronic-phase restenosis. Further development of devices that can be used in the femoropopliteal artery is needed in light of this speculation. .

The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial.

BACKGROUND: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. METHODS: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. RESULTS: One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. CONCLUSIONS: The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.

[Guiding significance of pathological diagnosis in watch and wait strategy for locally advanced rectal cancer patients after neoadjuvant therapy].

Some studies have demonstrated promising results of watch and wait (W&W) approaches in carefully selected patients with locally advanced rectal cancer who get a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT). This approach of organ- preservation helps patients avoid surgery and its related morbidity and mortality. nCRT will lead to the regression of the tumor cells and the uneven distribution of the residual tumor cells. The reliability of biopsy is still unsatisfactory in W&W strategy due to the high ratio of false negative cases. Therefore, the patients with negative histopathological assessment should also receive a strict follow-up. In the future, immune microenvironment and molecular markers, patient derived organoid, circulating tumor cells (CTCs) and circulating cell-free nucleic acids (cfDNA) may be helpful for screening and monitoring patients undergoing W&W.

Calculating the Tumor Nuclei Content for Comprehensive Cancer Panel Testing.

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.

Pathological evaluation of radiotherapy and concomitant intraarterial cisplatin for maxillary sinus cancer.

OBJECTIVE: Since 2010, we have mainly performed surgical treatment following radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for locally advanced maxillary sinus cancer (MSC). The present study investigated treatment results and pathological evaluations following RADPLAT for MSC. METHODS: Pathological response to RADPLAT was evaluated using surgical specimens. Pathological response was graded in accordance with the classification method that Shimosato reported in 1964, as grade V (no tumor cells remain in any of section), grade IV, III, II, I, and 0. Five-year overall and disease-specific survival rates were estimated using Kaplan-Meier methods. Univariate analyses of correlations between recurrence of MSC and other clinicopathological parameters were evaluated using the chi-square or Fisher's exact tests. RESULT: 19 patients were enrolled in this study, 5 patients showed T3 disease and 14 had T4 disease. One patient demonstrated local recurrence and 3 patients experienced distant metastasis. The 5-year overall survival rate was 67.1% (T3, 50.0%; T4, 69.6%), and the 5-year disease-specific survival rate was 81.9% (T3, 100%; T4, 76.0%). Histological response was categorized as grade V in 9 cases. No significant risk factors for residual cancer were identified. CONCLUSION: Our study suggested that RADPLAT not only has a low risk of side effects, but also could represent an effective procedure for locally advanced MSC by pathological evaluation. Increasing the therapeutic intensity of RADPLAT might provide an effective modality to avoid highly invasive surgery.

A Phase I clinical trial of carbon ion radiotherapy for Stage I breast cancer: clinical and pathological evaluation.

Even with its high RBE and >20 years history, there had been no breast cancer clinical trial using carbon-ion radiotherapy. We started a Phase I trial of carbon ion radiotherapy for Stage I breast cancer in 2013. This article describes the clinical and pathological evaluation of this study. Patients with low-risk Stage I breast cancer were eligible. A dose escalation study was designed, with dose levels of 48.0, 52.8 or 60.0 Gy relative biological effectiveness (RBE) administered in four fractions within 1 week. Three months after radiotherapy, the patients underwent tumor excision for pathological evaluation. Between April 2013 and December 2014, three cases receiving 48 Gy (RBE), three cases receiving 52.8 Gy (RBE) and one case receiving 60 Gy (RBE) underwent this protocol. No adverse effects were observed except for Grade 1 acute skin reaction in four cases. Pathological evaluation revealed that all four cases with doses of 52.8 Gy (RBE) and 60.0 Gy (RBE) achieved Grade 2b or more, but only two cases reached Grade 3. At the end of 2017, all cases were alive without recurrence or late had not caused any late adverse reaction. Carbon ion radiotherapy for Stage I breast cancer seems to be safe, and we found that it did not reach enough treatment effect 3 months after the treatment.

Pathological assessment of cytoreductive surgery specimens and its unexplored prognostic potential-a prospective multi-centric study.

BACKGROUND AND AIM: The grade/histological subtype is one of the most important prognostic markers in patients undergoing cytoreductive surgery (CRS). Our aim was to study other potential prognostic information that can be derived from the pathological evaluation of CRS specimens and provide a broad outline for evaluation of these. METHODS: This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). A protocol for pathological evaluation was laid down which was based on existing practices at the participating centers and included evaluation of the pathological PCI, regional node involvement, response to chemotherapy, morphology of peritoneal metastases (PM) and distribution in the peritoneal cavity. RESULTS: In 191 patients undergoing CRS at 4 centers, the pathological and surgical PCI differed in over 75%. Nodes in relation to peritoneal disease were positive in 13.6%. Disease in normal peritoneum adjacent to tumor nodules was seen in >50% patients with ovarian cancer and mucinous apppendiceal tumors. 23.8% of evaluated colorectal PM patients had a complete response and 25.0% ovarian cancer patients had a near complete pathological response to chemotherapy. CONCLUSIONS: Pathological evaluation of extent and distribution of peritoneal disease differs from the surgical evaluation in majority of the patients. Lymph node involvement in relation of peritoneal disease is common. The morphological presentation of PM in ovarian cancer and mucinous appendiceal tumors merits evaluation of more extensive resections in these patients. Standardized methods of synoptic reporting of CRS specimens could help capture vital prognostic information that may in future influence how these patients are treated.

Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis.@*METHODS@#A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively.@*RESULTS@#23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001).@*CONCLUSION@#Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.