Pancreatic juice cytology for diagnosing invasive pancreatic carcinoma/high-grade pancreatic intraepithelial neoplasia without visible tumors on endoscopic ultrasound.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most cases present only indirect imaging findings without visible tumors on endoscopic ultrasound (EUS). Therefore, EUS-guided fine-needle aspiration/biopsy is not applicable. An alternative diagnostic method is pancreatic juice cytology (PJC) via endoscopic naso-pancreatic drainage (ENPD-PJC), which is not the standard practice. This study aimed to investigate ENPD-PJC for diagnosing suspected PDAC/HG-PanIN cases without visible tumors on EUS. METHODS: Data of patients with suspected PDAC/HG-PanIN without visible tumors who underwent PJC were retrospectively evaluated. One PJC sample was collected during endoscopic retrograde pancreatography (ERP-PJC), and 12 samples were collected during ENPD-PJC, 3-hourly for cytological analysis. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC positivity indicated cytologically positive samples. Patients with positive/negative PJC with follow-up for <4-years were excluded as undiagnosed cases. A non-malignant diagnosis was based on histopathological absence/stable imaging findings for ≥4-years. The primary endpoint was to demonstrate that ERP/ENPD-PJC has a higher diagnostic ability than ERP-PJC. RESULTS: Twenty-two patients with histopathologically diagnosed PDAC/HG-PanIN and 31 with a non-malignant diagnosis were enrolled. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC showed sensitivities of 36.4 %, 86.4 %, and 77.3 %, specificities of 93.5 %, 87.1 %, and 93.5 %, and accuracies of 69.8 %, 86.7 %, and 86.7 %, respectively. ERP/ENPD-PJC and ENPD-PJC demonstrated superior sensitivity and accuracy compared to ERP-PJC. A greater occurrence of positive outcomes markedly distinguished true positives from false positives. CONCLUSIONS: ERP/ENPD-PJC and ENPD-PJC had higher diagnostic accuracies for PDAC/HG-PanIN without visible tumors on EUS. ENPD-PJC is recommended for the diagnosis of these lesions.

Genomic landscape of comprehensive genomic profiling in patients with malignant solid tumors in Japan.

BACKGROUND: Comprehensive genomic profiling (CGP) can aid the discovery of clinically useful, candidate antitumor agents; however, the variant annotations sometimes differ among the various types of CGP tests as well as the public database. The aim of this study is to clarify the genomic landscape of evaluating detected variants in patients with a malignant solid tumor. METHODS: The present, cross-sectional study used data from 57,084 patients with a malignant solid tumor who underwent CGP at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 1, 2019 and August 18, 2023. The pathogenicity of the variants was annotated using public databases. RESULTS: As a result of re-annotation of the detected variants, 20.1% were pathogenic and 1.4% were benign. The mean number of pathogenic variants was 4.30 (95% confidence interval: 4.27-4.32) per patient. Of the entire cohort, 5.7% had no pathogenic variant. The co-occurrence of the genes depended on the tumor type. Germline findings were detected in 6.2%, 8.8%, and 15.8% of the patients using a tumor/normal panel, tumor-only panel, and liquid panel, respectively, with the most common gene being BRCA2 followed by TP53 and BRCA1. CONCLUSIONS: The detected variants should be re-annotated because several benign variants or variants of unknown significance were included in the CGP, and the genomic landscape derived from these results will help researchers and physicians interpret the results of CGP tests. The method of extracting presumptive, germline, pathogenic variants from patients using a tumor-only panel or circulating tumor DNA panel requires improvement.

Clinicopathological characteristics of Lynch-like syndrome.

BACKGROUND: Lynch-like syndrome (LLS) has recently been proposed as a third type of microsatellite instability (MSI) tumor after Lynch syndrome (LS) and sporadic MSI colorectal cancer (CRC) without either a germline variant of mismatch repair (MMR) genes or hypermethylation of the MLH1 gene. The present study aimed to clarify and compare the clinicopathological characteristics of LLS with those of the other MSI CRC subtypes. METHODS: In total, 2634 consecutive patients with CRC who underwent surgical resection and subsequently received universal tumor screening (UTS), including MSI analysis were enrolled between January 2008 and November 2019. Genetic testing was performed in patients suspected of having Lynch syndrome. RESULTS: UTS of the cohort found 146 patients with MSI CRC (5.5%). Of these, excluding sporadic MSI CRC, 30 (1.1%) had a diagnosis of LS, and 19 (0.7%) had no germline pathogenic variants of the MMR gene. The CRC type in the latter group was identified as LLS. LLS occurred significantly more often in young patients, was left-sided, involved a KRAS variant and BRAF wild-type, and had a higher concordance rate with the Revised Bethesda Guidelines than sporadic MSI CRC. No significant differences were observed in terms of the clinicopathological factors between LLS and LS-associated MSI CRC; however, LLS had a lower frequency of LS-related neoplasms compared with LS. CONCLUSIONS: Distinguishing clinically between LS and LLS was challenging, but the incidence of neoplasms was higher in LS than in LLS, suggesting the need for different screening and surveillance methods for the two subtypes.

KDM2B-Rearranged Soft Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma.

Sarcomas with BCOR genetic alterations (BCOR-associated sarcomas) represent a recently recognized family of soft tissue and bone tumors characterized by BCOR fusion, BCOR internal tandem duplication, or YWHAE::NUTM2B fusion. Histologically, the tumors demonstrate oval to spindle cell proliferation in a variably vascular stroma and overexpression of BCOR and SATB2. Herein, we describe 3 soft tissue sarcomas with KDM2B fusions that phenotypically and epigenetically match BCOR-associated sarcomas. The cases included 1 infant, 1 adolescent, and 1 older patient. All tumors showed histologic findings indistinguishable from those of BCOR-associated sarcomas and were originally diagnosed as such based on the phenotype. However, none of the tumors had BCOR or YWHAE genetic alterations. Instead, targeted RNA sequencing identified in-frame KDM2B::NUTM2B, KDM2B::CREBBP, and KDM2B::DUX4 fusions. KDM2B fusions were validated using reverse-transcription PCR, Sanger sequencing, and in situ hybridization assays. Genome-wide DNA methylation analysis matched all 3 tumors with BCOR-associated sarcomas using the Deutsches Krebsforschungszentrum (DKFZ) classifier and t-distributed stochastic neighbor embedding analysis. One localized tumor showed a flat genome-wide copy number profile, and the patient remained disease-free after treatment. The other tumors showed multiple copy number alterations, including MDM2/CDK4 amplification and/or CDKN2A/B loss, and both tumors metastasized, leading to the patient's death in one of the cases. When tested using KDM2B immunohistochemistry, all 3 KDM2B-rearranged sarcomas showed diffuse strong staining, and all 13 sarcomas with BCOR genetic alterations also demonstrated diffuse, strong, or weak staining. By contrast, among 72 mimicking tumors, only a subset of synovial sarcomas showed focal or diffuse weak KDM2B expression. In conclusion, our study suggests that KDM2B-rearranged soft tissue sarcomas belong to the BCOR-associated sarcoma family and expand its molecular spectrum. This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.

Pancreatic duct epithelial malignancy suggested by large focal pancreatic parenchymal atrophy in cystic diseases of the pancreas.

BACKGROUND: /Objectives: A cystic lesion is common in the pancreas. Focal pancreatic parenchymal atrophy (FPPA) has been reported as a sign of high-grade pancreatic intraepithelial neoplasia/carcinoma in situ (HGP/CIS). Some cystic lesions accompany FPPA. However, the relationship between a cystic lesion, FPPA, and the histopathological background of the pancreatic duct is unknown. METHODS: We retrospectively evaluated the data of 98 patients with a cystic lesion who underwent serial pancreatic juice aspiration cytologic examination (SPACE) because of accompanying FPPA, increased size of the cystic lesion, and pancreatic duct stricture at the base. RESULTS: The clinical diagnosis of a cystic lesion was intraductal papillary mucinous neoplasia (IPMN) and cysts in 72 (73.5%) and 26 (26.5%) patients, respectively. Ninety of the 98 patients (91.8%) had FPPA. Positive results (adenocarcinoma and suspicion) on SPACE were observed in 56 of all cases (57.1%), 48 of IPMN (66.7%), 8 of cysts (30.8%), and 54 of FPPA (59.3%), and were significantly associated with IPMN (p = 0.002) and the large FPPA (>269.79 mm2,p = 0.0001); moreover, these disorders are considerably related (p = 0.0003). Fifty patients (51.0%) with positive results on SPACE underwent surgery, with the histopathological diagnosis of epithelial malignancy in 42 patients (42.9%, 42/50, 84%). Many cystic lesions clinically diagnosed as IPMN were dilated branches covered by pancreatic intraepithelial neoplasia. CONCLUSIONS: Positive results on SPACE were significantly associated with the clinical diagnosis of IPMN and the large FPPA. Moreover, these disorders are significantly related. Surgery owing to positive results could lead to the histopathological diagnosis of HGP/CIS.

[Curative Resection after Chemotherapy for Advanced Extensive Cholangiocarcinoma-A Case Report].

A 73-year-old, male patient presented with the chief complaint of epigastric pain and received the diagnosis of extensive cholangiocarcinoma after a close examination. Extensive extension of the malignancy into the right and left hepatic ducts precluded a curative resection, and the patient received GC therapy. After 11 courses of GC over about 1 year, no new lesions or tumor progression was observed, and a bile duct mapping biopsy was performed to investigate the possibility of resection conversion. The results showed a marked decrease in atypia, and reactive atypia was diagnosed. A pancreaticoduodenectomy was performed, and histopathologically negative margins were obtained. The response to treatment was Grade Ⅱa according to the Evans classification. At 23 months after the start of treatment and 12 months after surgery, the patient is recurrence-free without adjuvant chemotherapy. Although the evidence for conversion surgery for biliary tract cancer has not been established, the long-term outcomes may be favorable.

[A Case of a Two-Stage Robotic-Assisted Surgery for a Neuroendocrine Tumor of the Pancreatic Tail with Simultaneous Single Liver Metastasis].

As medical insurance coverage for robotic surgery has been expanded in the field of gastrointestinal surgery in Japan, the number of cases undergoing robotic surgery for hepato-biliary-pancreatic disease has been increasing. Therefore, cases with malignant tumors and metastatic lesions tend to undergo robotic operation for both primary tumors and metastases. Herein, we report a case of neuroendocrine tumor(NET)in the pancreatic tail with simultaneous single liver metastasis, which was treated with two-stage robotic-assisted surgery. A 67-year-old female underwent a computed tomography scan and a hypovascularized tumor in the pancreatic tail region and liver was found. A biopsy of the pancreatic tumor by endoscopic ultrasound-guided fine needle aspiration demonstrated a NET G1-2. The liver lesion was diagnosed as a metastatic tumor, considering the other examinations. The patient underwent a robotic distal pancreatectomy(RDP)and was histopathologically diagnosed as NET G2. Sixty-three days after the RDP, a two-stage partial liver resection for the metastatic tumor was performed under robotic assistance. Curative resection was achieved through two-stage robot-assisted surgery, there were no postoperative complications.

Focal pancreatic parenchyma atrophy is a harbinger of pancreatic cancer and a clue to the intraductal spreading subtype.

BACKGROUND/OBJECTIVES: Radiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis. METHODS: Data on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC. RESULTS: FPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P < 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16-63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved. The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P < 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia. CONCLUSIONS: FPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.

Upper gastrointestinal tumors are unrelated to the APC genotype in APC-associated polyposis.

BACKGROUND: In patients with APC-associated polyposis, the prevalence of upper gastrointestinal tumors and the relationship between these and Helicobacter pylori infection have not been clarified in detail. The present study aimed to clarify the features of upper gastrointestinal lesions in patients with APC-associated polyposis. METHODS: Consecutive patients with APC-associated polyposis who underwent esophagogastroduodenoscopy between 2004 and 2018 were recruited. RESULTS: In total, 36 patients were enrolled. The types of gastrointestinal tumor observed were fundic gland polyposis in 28 patients (77.8%), gastric adenoma in 15 patients (41.7%), duodenal adenoma in 27 patients (75.0%) and periampullary adenoma in 20 patients (55.6%). The phenotype of these upper gastrointestinal tumors was not necessarily the same in patients belonging to the same family. Germline variants in the APC gene were distributed across various sites, regardless of the presence or absence of upper gastrointestinal lesions, and none of the tumors correlated with the genotype or phenotype of upper gastrointestinal tumors. Fundic gland polyposis was observed in 28 of 31 patients without a H. pylori infection and in none of the patients with a H. pylori infection (P = 0.00015). After eradication therapy for H. pylori, fundic gland polyposis developed in one, previously infected patient. CONCLUSION: The upper gastrointestinal tumor phenotype was not associated with the genotype in patients with APC-associated polyposis. Ascertaining the H. pylori infection status is helpful for endoscopic surveillance of upper gastrointestinal tumors in patients with APC-associated polyposis.

Central nervous system mucormycosis in a patient with hematological malignancy: A case report and review of the literature.

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day -11 and complained of aphasia and right hemiparesis on day -6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis.

Fusobacterium nucleatum load in MSI colorectal cancer subtypes.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) infection may lead to colorectal cancer (CRC) development in the context of microsatellite instability (MSI). To date, however, the relationship between F. nucleatum load and MSI CRC subtypes has not been clarified. METHODS: One hundred seventy-nine consecutive patients with CRC were enrolled in the present study. In 94 patients with MSI CRC, 32 had hereditary MSI CRC from Lynch syndrome, 62 had sporadic MSI CRC, while the remaining 85 had microsatellite stable (MSS) CRC. The association of the F. nucleatum load with each CRC subtype and the patients' clinicopathological characteristics was examined. RESULTS: Of the 179 patients with CRC, 158 (88.3%) were F. nucleatum-positive. A high F. nucleatum load was found in 84.4% (27/32), 96.8% (60/62), and 83.5% (71/85) of the patients with hereditary MSI CRC, sporadic MSI CRC, and MSS CRC, respectively (P = 0.024). In terms of clinicopathological features, a high F. nucleatum load was significantly associated with female, right-sided CRC, BRAF V600E, CpG island methylator phenotype-positive CRC, and MSI CRC (P = 0.008, P = 0.015, P = 0.007, P = 0.006, and P < 0.001, respectively). However, the clinicopathological characteristics did not differ significantly by F. nucleatum load between hereditary and sporadic MSI CRCs without tumor depth. CONCLUSIONS: The F. nucleatum load was higher in hereditary MSI CRC than in MSS CRC as well as sporadic MSI CRC. These findings may contribute to preventing CRC in hereditary MSI CRC through appropriate intervention.

Short- and long-term outcomes of immediate breast reconstruction surgery after neoadjuvant chemotherapy.

PURPOSE: Immediate breast reconstruction (IBR) is a standard option for breast cancer patients, although its utility in patients with advanced breast cancer requiring neoadjuvant chemotherapy (NAC) is debatable. We assessed the short-term complications and long-term prognosis of IBR after NAC. METHODS: We retrospectively analyzed 1135 patients with IBR and/or NAC between 2010 and 2018, 43 of whom underwent IBR after NAC. RESULTS: Twenty-five patients underwent reconstruction with a tissue expander (TE) followed by silicon breast implantation, 5 with a latissimus dorsi muscle transfer flap, and 13 with a deep inferior epigastric perforator flap. Complete surgical resection with a free margin confirmed by a pathological assessment was achieved in all patients. The evaluation of the short-term complications indicated no cases of total flap necrosis, two cases of partial flap necrosis, and one case of wound infection. Only one case required postponement of subsequent therapy due to partial flap necrosis. A long-term evaluation indicated no local recurrence, although distant metastasis was observed in 4 cases, 3 patients died, and TE removal after post-mastectomy radiotherapy (PMRT) was performed in 2 of 11 TE cases. CONCLUSION: IBR may be a viable option in patients with advanced breast cancer who achieve complete surgical resection after NAC.

[Treatment Strategies for Liver Oligometastases of Esophageal Cancer].

Benefits of local therapy for liver oligometastases of esophageal cancer has not been established. There are 2 cases of resection for liver oligometastases of esophageal cancer. Case 1: A 65-year-old male diagnosed with liver metastasis of esophageal cancer 12 months after initial treatment. A tumor located in segment 7 was resected after 6 months of chemotherapy. Case 2: A 71-year-old female diagnosed with liver metastasis of esophageal cancer 14 months after initial treatment. During 6 months of chemotherapy, tumor diameter increased but there were no new lesions. The tumor located in segment 8 was resected. In both cases, R0 resection was performed without intraoperative injury to the reconstructed esophagus. They had a recurrence free survival of more than 5 months. Resection of liver metastasis of esophageal cancer may be useful in combination with drug therapy in case it was diagnosed with liver oligometastases.

Surgical upstaging rates in patients meeting the eligibility for active surveillance trials.

PURPOSE: Four clinical active surveillance trials including LORIS, COMET, LORD and LORETTA, are being conducted to assess whether women with low-risk ductal carcinoma in situ can safely avoid surgery. The present study aimed to determine the rate of upstaging to invasive cancer among patients with a preoperative diagnosis of ductal carcinoma in situ and to evaluate the incidence of upstaging in patients meeting the eligibility criteria for four active surveillance clinical trials. METHODS: The present study initially enrolled 180 patients with 183 calcifications who received the diagnosis of ductal carcinoma in situ by biopsy. Patients were classified as eligible for four clinical trials according to the respective inclusion criteria. RESULTS: In total, 152 patients with 155 calcifications were analyzed. Of these, 32 (21%) were upstaged to invasive disease based on the final pathological analysis of surgical specimens. Of the 152 patients, 53 (35%), 90 (59%), 24 (16%) and 34 (22%) met the eligibility criteria for the LORIS, COMET, LORD and LORETTA trial, respectively. Among patients with low-risk ductal carcinoma in situ, 10 (19%), 14 (16%), 6 (25%) and 4 (12%) patients were upstaged to invasive disease in LORIS, COMET, LORD and LORETTA, respectively. The upstaging to pT1b or higher rates were 2% (1/53), 3% (3/90), 0% (0/24) and 3% (1/34) in LORIS, COMET, LORD and LORETTA, respectively. CONCLUSIONS: The upstaging rate in patients eligible for the clinical active surveillance trials was 12-25%. Although the rate of upstaging to pT1b or higher was low, further studies are required to determine the rates of upstaging to invasive cancer and the risk factors among patients with low-risk ductal carcinoma in situ.

Clinicopathological features of sporadic MSI colorectal cancer and Lynch syndrome: a single-center retrospective cohort study.

BACKGROUND: The clinical and pathological features of sporadic microsatellite instability-high (MSI) colorectal cancer (CRC) are still unclear. The present study aimed to clarify the clinicopathological features of sporadic MSI CRC in comparison with those of Lynch syndrome (LS) exploratorily. METHODS: The present study was a single-center, retrospective cohort study. Sporadic MSI CRC was defined as MSI CRC with aberrant promoter hypermethylation of the MLH1 gene, while hereditary MSI CRC was defined colorectal cancer in patients with LS. RESULTS: In total, 2653 patients were enrolled; of these, 120 (4.5%) had MSI CRC, 98 had sporadic MSI CRC, and 22 had LS. Patients with sporadic MSI CRC were significantly older (p < 0.001) than those with LS and had a right-sided colonic tumor (p < 0.001) which was pathologically poorly differentiated or mucinous (p = 0.025). The overall survival rate was significantly lower in patients with stage I, II or III MSI CRC than in those with LS (p = 0.024). However, the recurrence-free survival rate did not differ significantly (p = 0.85). CONCLUSIONS: We concluded that patients with sporadic MSI are significantly older, tumors more likely to locate in the right-sided colon, pathologically poorly differentiated or mucinous, and worse overall survival than in those with LS.

Distribution of Transplantation-Associated Thrombotic Microangiopathy (TA-TMA) and Comparison between Renal TA-TMA and Intestinal TA-TMA: Autopsy Study.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an important complication of hematopoietic stem cell transplantation. To date, information regarding the organs that are affected by TA-TMA as confirmed histologically remains limited; the clinicopathologic differences between renal TA-TMA and intestinal TA-TMA have not been examined despite being the well-known and commonly affected sites of TA-TMA. We therefore examined 165 autopsied patients after hematopoietic stem cell transplantation and compared the clinicopathologic factors of renal and intestinal TA-TMA. It was clear that 38 (23%) of our patients had TA-TMA. In the TA-TMA cases, the kidney (61%) and intestine (53%) were commonly affected, and the ileum and right colon were vulnerable. Other organs that we found to be affected by TA-TMA included the stomach (8%), gallbladder (5%), and oral cavity, pharynx, esophagus, liver, heart, urinary bladder, and ureter (all at 3%), and symptoms thought to be caused by TA-TMA of these organs were not observed in any patient. Histologically, TA-TMA only affected the arteriole, or small arteries, regardless of the organ, and the veins or larger arteries were not affected at all. In the kidney, the glomerular capillary was also affected, and mesangiolysis and double contours of the basement membranes were often in evidence. The histologic overlap of renal and intestinal TA-TMA was rare (13%), and the patients in the intestinal TA-TMA group exhibited more frequency of a history of intestinal acute graft-versus-host disease (GVHD) during the clinical course compared with that of the renal TA-TMA group (80% versus 22%, P = .0016). Although TA-TMA can affect many other organs, the frequency of these ancillary events was low, and the clinical effect may have been small. Our results suggest that in comparison to renal TA-TMA, intestinal GVHD could be more closely associated with intestinal TA-TMA as a risk factor.

Focal parenchymal atrophy of pancreas: An important sign of underlying high-grade pancreatic intraepithelial neoplasia without invasive carcinoma, i.e., carcinoma in situ.

OBJECTIVES: Diagnosing high-grade intraepithelial neoplasia without invasion, traditionally referred to as carcinoma in situ (CIS), is essential for improving prognosis. We examined the imaging findings of patients with and without CIS to identify significant aspects for the diagnosis of CIS. METHODS: Forty-six patients strongly suspected of early pancreatic cancer without nodule on imaging (CIS group, n = 27; non-malignant group, n = 19) were retrospectively evaluated according to ten factors of computed tomography/magnetic resonance imaging (CT/MRI), endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) using hierarchical cluster and univariate analyses. RESULTS: Two clusters were formed by hierarchical cluster analysis. One cluster consisted of 83.3% CIS cases with similar image findings such as focal pancreatic parenchymal atrophy (FPPA) on CT/MRI, main pancreatic duct (MPD) stricture surrounded by hypoechoic areas on EUS, and MPD stricture with upstream MPD dilation on ERCP. On univariate analysis, the CIS and non-malignant groups had FPPA on CT/MRI in 15 (55.6%) and 3 (15.8%) cases (p = 0.013), and MPD stricture surrounded by hypoechoic areas on EUS in 20 (74.1%) and 4 (21.1%) cases (p = 0.001), respectively. MPD stricture surrounded by hypoechoic areas was observed in 80% (12/15) of CIS cases with FPPA on CT/MRI and correlated with FPPA. Moreover, FPPA and MPD stricture surrounded by hypoechoic areas had histopathologically observed fibrosis or fat replacement due to pancreatic parenchymal atrophy. CONCLUSIONS: FPPA and MPD stricture surrounded by hypoechoic areas are significant findings for the diagnosis of CIS.

False-negative ultrasound-guided fine-needle aspiration of axillary lymph nodes in breast cancer patients.

INTRODUCTION: The purpose of this study was to clarify the clinicopathological features of patients with false-negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. METHODS: Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2 mm) group and macrometastasis (>2 mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. RESULTS: A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non-SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. CONCLUSIONS: The false-negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false-negative FNAC results.

Predictive factors of an axillary pathological complete response of node-positive breast cancer to neoadjuvant chemotherapy.

PURPOSE: The present study aimed to identify the predictive factors of an axillary pathological complete response (Ax-pCR) in patients with node-positive breast cancer who underwent neoadjuvant chemotherapy (NAC). METHODS: The present study included 219 patients who underwent NAC followed by curative surgery, including axillary lymph node dissection (ALND), for 221 breast cancers between January 2010 and April 2018. All patients were clinically and/or pathologically confirmed to be node-positive at the initial diagnosis. The predictive factors of Ax-pCR were analyzed using a chi-square test and multivariate logistic regression models. RESULTS: Ninety-five patients (43%) achieved Ax-pCR after NAC. The odds of achieving Ax-pCR were significantly improved when tumors were high grade (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.00-4.84), estrogen receptor (ER) negative (OR 2.65 95% CI 1.23-5.70), ycN0 on ultrasound (US) imaging (OR 3.89, 95% CI 1.90-7.97), and showed a clinical complete response (CR) at the primary site after NAC (OR 4.22, 95% CI 1.59-11.27). CONCLUSIONS: Ax-pCR was more likely to be achieved in patients who were diagnosed with ER-negative and high-grade breast cancer and those with ycN0 and clinical CR at the primary site after NAC than among others. Among these patients, those with initially cN1/N2 might be good candidates for a deescalated treatment strategy after NAC.

[Successful Surgical Resection of Expansive-Growth Acinar Cell Carcinoma-A Case Report].

Here, we report a case of successful surgical resection of expansive-growth acinar cell carcinoma. A 59-year-old man was referred to a local hospital with abdominal distention. CT revealed a large abdominal tumor. Subsequently, he was referred to our hospital. Physical examination showed a large tumor on his left upper abdomen without tenderness. CT revealed an enhanced 18 cm-sized expansive-growth tumor on the left flank, suggesting a primary pancreatic tumor. EUS-FNA yielded a diagnosis of adenocarcinoma. Imaging findings were not typical for pancreatic ductal carcinoma. We performed distal pancreatectomy with splenectomy, transverse colon resection, and proximal gastrectomy. Pathological findings revealed a tumor, measuring 19.5×16.5×15.5 cm, originating from the pancreatic body, positive for trypsin, chymotrypsin, and elastase, consistent with a diagnosis of acinar cell carcinoma, pT3, N0, M0. Four courses of adjuvant chemotherapy with S-1 were provided, and the patient is currently alive without recurrence for 10 months.