Feasibility of high-frequency ultrasound for seminiferous tubule assessment and correlation of B-mode imaging with pathological findings in the testis in azoospermia.

PURPOSE: To determine the feasibility of high-frequency ultrasound (HFUS) for assessing seminiferous tubules and to understand high-resolution B-mode images of the testes in cases of azoospermia. METHODS: We verified how the histopathological images of testicular biopsy specimens can be observed using HFUS images and measurement analysis of seminiferous tubules was performed to 28 testes of 14 cases with azoospermia who underwent preoperative ultrasound and microdissection testicular sperm extraction (micro-TESE). The population consisted of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), including Sertoli cell-only syndrome (SCOS), and the other pathologies. Statistical verification of differences in seminiferous tubule diameters among preoperative ultrasound examination, ultrasound examination of pathological specimens, and histopathological specimens. We also examined the imagingpathology correlation via a case series presentation, aiming to identify imaging markers of testicular pathology and determine the possibility of predicting each condition. RESULTS: A comparison between HFUS images and histopathology from the same biopsy specimens suggested that ultrasonography could be seen as stereoscopic images due to its significantly greater slice thickness. The diameters of tubules were generally larger in pathological tissues as compared to ultrasonographic findings in OA and SCOS, but not in the other conditions. Comparisons provided insights into the predictability of SCOS and revealed imaging findings such as gaps between tubules and decreased diameter reflective of testicular damage. CONCLUSION: Seminiferous tubules can be observed however the diameter of seminiferous tubules varies in imaging and histopathology depending on the pathology. Imaging findings that reflect testicular damage and the predictability of SCOS were revealed in this study, but further verification is required.

Case report: A case of acute exacerbation of interstitial pneumonia associated with TAFRO syndrome.

Cytokine storm caused by the overproduction of inflammatory interleukin (IL)-6 plays a central role in the development of acute inflammation. The extremely rare disease, TAFRO syndrome, progresses quickly. Renal dysfunction, fever, reticulin fibrosis, anasarca, thrombocytopenia, and organomegaly with pathological findings such as idiopathic multicentric Castleman disease are all characteristics of TAFRO syndrome. Interstitial pneumonia (IP), which is not characteristic of this disease, is probably a complication of the inflammatory process. An 88-year-old man presented with a 3-day history of fever, dry cough, and progressive dyspnea. After he was first treated with antibiotics, he was transferred to our hospital because he showed no improvement. Data showed hemoglobin Hb 90.00 (SI) (9.0 g/dL); leukocyte count WBC 23 × 109/L (SI) [23,000/µL (neutrophils 87.5%, lymphocytes 2.5%, blast cells 0%)]; hemoglobin 90 g/L (9.0 g/dL); platelet count 101.00 × 109/L (10 100/µL); lactate dehydrogenase 4.78 µkat/L (286 U/L); serum albumin 25.00 g/L (2.5 g/dL); blood urea nitrogen 18.17 µmol/L (50.9 mg/dL); creatinine 285.53 µmol/L (3.23 mg/dL); C-reactive protein 161.50 mg/L (16.15 mg/dL); IL-61830 pg/mL; and surfactant protein D level 26.6 ng/mL. Findings from computed tomography indicated increased ground-glass opacities without traction bronchiectasis consistent with acute IP. The diagnosis was leukocytosis and progressive kidney injury. After bone marrow aspiration caused by persistent pancytopenia, mild reticulin fibrosis was identified. Because of the high IL-6 concentration, which revealed small atrophic follicles with regressed germinal centers surrounded by several lymphocytes, right inguinal lymph node biopsy was performed. Two minor and three major criteria led to diagnosis of TAFRO syndrome. Administrations of antibiotic therapy and methylprednisolone pulse therapy were ineffective. After rapid progress of respiratory failure, the patient died on day 30 of hospitalization. Autopsy of lung tissues showed diffuse alveolar damage with hyaline membranes. Based on these findings, we diagnosed acute exacerbation of IP associated with TAFRO syndrome due to IL-6 overproduction-associated cytokine storm.

Immunohistochemical analysis of the distribution of RANKL: a case of disseminated carcinomatosis of bone marrow as the first presentation of relapse in curatively resected colorectal cancer.

Poorly differentiated adenocarcinoma of colorectal carcinoma (CRC) is a rare condition with poor prognosis. In this report, we describe a case of a 69-year-old man who underwent laparoscopic low anterior resection after being diagnosed with stage IIIB CRC. At 10 months post-operation, he developed fever and loss of appetite. Laboratory examination revealed > 120.0 µg/dL fibrin degradation products and > 60.0 µg/dL D-dimer. Bone marrow (BM) examination showed malignant epithelioid infiltrate with CK20 and CDX2 expression, leading to diagnosis of disseminated carcinomatosis of BM, which is rare in CRC and indicative of widespread disease throughout the body. Furthermore, immunohistochemistry revealed high expression of receptor activator of nuclear factor κB ligand (RANKL) in tumor cells, including budding cells of CRC and BM tissues. Thus, RANKL expression, which is known to indicate metastatic behavior of cancer cells, may play a critical role in promoting osteoclast formation, which has been associated with the pathogenesis of BM lesions.

A case of hemophagocytic lymphohistiocytosis after BNT162b2 COVID-19 (Comirnaty®) vaccination.

RATIONALE: Coronavirus disease (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was reported in Wuhan of China in December 2019. The world is still in a state of pandemic owing to COVID-19. COVID-19 vaccines help our bodies develop immunity against the virus that causes COVID-19 without having to get the illness. Herein, we describe a rare case of a critical disorder, hemophagocytic lymphohistiocytosis (HLH), in a patient with nephritic sclerosis associated with hypertension, following mRNA COVID-19 vaccination. HLH is a life-threatening hyperinflammatory syndrome caused by aberrantly activated macrophages and cytotoxic T cells that may rapidly progress to terminal multiple organ failure. PATIENT CONCERNS: An 85-year-old Japanese woman with chronic renal failure and hypertension was included in this study. Routine laboratory investigations provided the following results: white blood cell (WBC) count, 4.6 × 109/L; hemoglobin (Hb), 8.1 g/dL; platelet count, 27 × 109/L; blood urea nitrogen 48.9 mg/dL, and serum creatinine 3.95 mg/dL. The patient developed malaise, vomiting, and persistent high fever (up to 39.7°C) on the 12th day after receiving the second dose of the vaccine. Initial evaluation revealed neutropenia. The total WBC count was 0.40 × 109/L (Neutrophils 0, Lymphocytes 240/µ, blast 0%); Hb 9.0 g/dL, platelet count 27 × 109/L; and, C Reactive Protein 9.64 mg/dL. DIAGNOSIS: Further tests showed hyperferritinemia (serum ferritin 2284.4 µg/L). Bone marrow examination revealed haemophagocytosis. A provisional diagnosis of HLH associated with the Comirnaty® vaccination was made based on the HLH-2004 diagnostic criteria. INTERVENTIONS: The patient was treated with granulocyte colony-stimulating factor and 500 mg methylprednisolone. OUTCOMES: A significant improvement was observed in the patient's condition; the abnormal laboratory results resolved gradually, and the patient was discharged. LESSONS: This case serves to create awareness among clinicians that HLH is a rare complication of COVID-19 vaccination and should be considered, especially in patients with a history of chronic renal failure and hypertension.

Acute respiratory distress syndrome due to sepsis caused by Bacteroides ovatus after acute appendicectomy.

BACKGROUND: Appendicectomy is generally a minimally invasive surgery, after which postoperative complications such as acute respiratory distress syndrome (ARDS) are rare. We describe a case of ARDS due to sepsis caused by Bacteroides ovatus after appendicectomy. CASE PRESENTATION: A man in his 60 s presented to our hospital with a chief complaint of right lower quadrant abdominal pain. He was diagnosed with acute appendicitis and underwent emergency laparoscopic appendicectomy. Cefmetazole was administered as a perioperative antibacterial drug. Postoperatively, the abdominal findings improved. However, on postoperative day three, bloody sputum and respiratory distress were observed. We performed thoracoabdominal computed tomography (CT) and observed bilateral pleural effusion and mottled frosted glass shadows extending to both lung fields. ARDS was diagnosed. We treated the patient with steroids and sivelestat sodium and switched the antibacterial drug to meropenem. The patient's general condition improved. After the patient was treated, Bacteroides ovatus was isolated from preoperative blood culture, which was resistant to cefmetazole. CONCLUSIONS: We encountered a case in which ARDS due to sepsis was caused by Bacteroides ovatus after acute appendicectomy. Blood culture to isolate the causative organism and determine its antimicrobial sensitivity after commencement of empiric antibiotics is important even in common diseases, such as acute appendicitis.

Nivolumab in combination with radiotherapy for metastatic esophageal neuroendocrine carcinoma after esophagectomy: a case report.

BACKGROUND: Metastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time. CASE PRESENTATION: A man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography-computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography-computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months. CONCLUSIONS: We experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.

Effect of Vitamin D Supplements on Relapse of Digestive Tract Cancer with Tumor Stromal Immune Response: A Secondary Analysis of the AMATERASU Randomized Clinical Trial.

The aim was to examine whether vitamin D supplementation (2000 IU/day) reduces the risk of relapse in a subgroup of patients with digestive tract cancer, showing a sufficient immune response in tumor stroma by conducting secondary subgroup analyses of the AMATERASU randomized, double-blind, placebo-controlled trial (UMIN000001977). A total of 372 patients were divided into two subgroups stratified by the median density of immune cells infiltrating in tumor stroma into higher and lower halves. In the higher-half subgroup of CD56+ cells, the relapse ratio was significantly lower in the vitamin D group (7.4%) than in the placebo group (20.5%) (subdistribution hazard ratio (SHR), 0.35; 95% confidence interval (CI), 0.15-0.82), but it was equivalent (25.2% vs. 22.7%) in the lower-half subgroup of CD56+ cells (SHR, 1.21; 95% CI, 0.68-2.19) with a significant interaction (Pinteraction = 0.02). Although there were no significant differences, the risk of relapse was lower in the vitamin D group than in the placebo group in the higher half of CD45RO+ memory T cells (8.9% vs. 19.2%), and of CD8+ cytotoxic T cells (11.3% vs. 22.5%). In patients with digestive tract cancer, vitamin D supplementation was hypothesized to reduce the risk of relapse in the subgroup of patients who already have an adequate infiltration of immune cells in their tumor stroma.

In vitro Demonstration of Melanoma Metastasis in Lymph Nodes of Prepared Specimens Using a Light-emitting Diode-based Multispectral Photoacoustic Ultrasound Imaging System.

Although an excellent photoacoustic (PA) ultrasound method has been reported for the evaluation of lymph node melanoma metastasis in animal experiments, it remains to be evaluated in clinical trials. Recently, we performed PA ultrasound assessment using light-emitting diodes to detect metastatic melanoma in the lymph nodes of specimens prepared for microscopic examination. The PA effect was not obvious in amelanotic melanoma, but was seen in melanotic melanoma by PA imaging (PAI) and histopathological correlation in cases of primary melanotic melanoma accompanied by metastatic lymph nodes, including the coexistence of amelanotic melanoma and melanotic melanoma. Clinical workup should be performed with not only PAI but also conventional ultrasonography in cases with metastasis related to amelanotic transformation, which would likely be missed by PAI alone.

Double percutaneous transesophageal gastrotubing precluded high risk surgery for intestinal malignant lymphoma.

Primary gastrointestinal lymphoma is relatively rare and typically treated by chemotherapy. In some cases, surgery for obstruction in the proximal small intestine is challenging and has a high risk for anastomotic leakage. An 80-year-old woman presented to our hospital with vomiting and abdominal distension. Enteroscopy showed a type 2 circumferential tumor in the proximal jejunum 6 cm on the anal side from Treitz ligament. Biopsy showed solid and diffuse proliferation of large atypical cells with round and irregular nuclei. On immunohistochemistry, these cells were positive for CD20, CD79a, and CD138. Diffuse large B-cell lymphoma (DLBCL) was diagnosed and classified as Ann Arbor stage IIE and Lugano classification stage II 2 and scored 1 point on the International Prognostic Index (i.e., low risk). Given the risk of anastomotic leakage due to lesions and residual obstructive enteritis, surgery was not performed. The patient received double percutaneous transesophageal gastrotubing (dPTEG) to facilitate decompression and enteral nutrition. Enteral nutrition and chemotherapy were initiated immediately after dPTEG insertion. After one course of rituximab plus cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP), the tumor showed a partial response, and the obstruction was improved. Oral ingestion was started, and the dPTEG tube was removed. After six courses of R-CHOP, enhanced CT, positron emission tomography-CT, and serum interleukin-2 levels indicated complete treatment response. During treatment, gastrointestinal perforation did not occur, oral intake was good, and careful follow-up will be continued. dPTEG for obstructive small intestinal DLBCL could help avoid high-risk surgery, and a complete response to chemotherapy was achieved.

Cronkhite-Canada Syndrome Successfully Treated by Corticosteroids before Presenting Typical Ectodermal Symptoms.

Cronkhite-Canada syndrome (CCS) is a rare disease characterized by diffuse gastrointestinal polyposis with chronic diarrhea and ectodermal change, but its etiology is unknown. We present a case at the age of 26 years complaining of epigastralgia and weight loss. Endoscopic examination revealed extensive diffuse polypoid lesions of the stomach and the terminal ileum, all of which showed hyperplastic polyps pathologically. There were no polypoid lesions in his colon. He has no family history of diffuse gastrointestinal polyposis. Diffuse gastrointestinal hyperplastic polyposis without any hereditary association led us to suspect this case as CCS although he did not show chronic diarrhea and any ectodermal symptoms such as onychodystrophy, alopecia, and hyperpigmentation. After initiation of a corticosteroid therapy, his epigastralgia disappeared and he gained appetite and weight, accompanied by normalization of serum albumin levels. Endoscopic examination 1 year after initiation of corticosteroid therapy revealed a decrease in the number of gastric polyposis and those inflammations. This rare young case may suggest that early therapeutic intervention with corticosteroids could improve the prognosis of CCS, preventing not only malnutrition but also appearance of several ectodermal symptoms.

Pembrolizumab plus platinum-based chemotherapy for unfavorable cancer of unknown primary site: Case report.

INTRODUCTION: We report a case of sustained complete response in unfavorable cancer of unknown primary site (CUP) successfully treated with chemotherapy combining pembrolizumab, pemetrexed and platinum. CASE PRESENTATION: A 66-year-old man was presented with weight loss and cough for 3 months. Contrast-enhanced computed tomography (CT) confirmed a mass in the superior anterior mediastinum and multiple enlarged mediastinal and axillary lymph nodes. Positron emission tomography-CT (PET-CT) showed abnormal uptake in the corresponding lesions. Histopathological analysis of the left axillary nodule revealed poorly differentiated adenocarcinoma. Immunohistochemistry showed the tumor cells were positive for cytokeratin 7 and thyroid transcription factor-1 and negative for cytokeratin 20. Thus, the patient was diagnosed as poorly differentiated adenocarcinoma of unknown primary, and treated as non-small-cell lung cancer. Additional genetic testing revealed the patient was negative for EGFR, ALK fluorescence in situ hybridization, ROS1, BRAF, and PD-L1 22C3 IHC with Tumor Proportion Score (TPS) was less than 1%. The patient received six cycles of pembrolizumab, platinum, and pemetrexed intravenously. Cisplatin was switched to carboplatin because of cisplatin nephrotoxicity in one course. PET-CT after six cycles showed all lesions disappeared; complete response was considered to have been achieved. Maintenance therapy of pembrolizumab and pemetrexed has been continued for 6 months after the induction therapies to prevent progressive disease. Complete response has been maintained. DISCUSSION: Chemotherapy with pembrolizumab, platinum and pemetrexed could be valuable for treating unfavorable CUP. CONCLUSION: Chemotherapy with pembrolizumab, platinum, and pemetrexed helped achieved sustained complete response in a patient with unfavorable CUP.

An Autopsy Case of Varicella Zoster Virus Encephalitis with Multiple Brain Lesions.

Varicella-zoster virus (VZV) encephalitis in the absence of vasculopathy may rarely occur in association with herpes zoster. We herein report the case of a 67-year-old woman with non-Hodgkin's lymphoma undergoing chemotherapy who presented with an acute alteration in consciousness. Magnetic resonance imaging of the brain revealed multiple and nonspecific lesions of hyperintensity with mild edema in the cortex and subcortex. She was treated with intravenous acyclovir. However, two days after admission, the patient died and was diagnosed with VZV encephalitis. This case highlights the risk of VZV reactivation with severe neurological complications in patients undergoing immunosuppressive therapy.

Effect of Vitamin D on Relapse-Free Survival in a Subgroup of Patients with p53 Protein-Positive Digestive Tract Cancer: A Post Hoc Analysis of the AMATERASU Trial.

BACKGROUND: The AMATERASU randomized trial of vitamin D3 supplementation (2,000 IU/day; UMIN000001977) showed the potential benefit of vitamin D in a subgroup of patients with digestive tract cancer. By conducting post hoc analyses of this trial, we further explored whether subgroups stratified by expression levels of p53, vitamin D receptor (VDR), and Ki-67 modify the effect of vitamin D supplementation. METHODS: The primary outcome was relapse-free survival (RFS). On IHC using pathologic specimens, the degree of p53 protein expression parallel with TP53 missense mutations was classified as p53 positive (>10%) and p53 negative (≤10%). In addition, VDR and Ki-67 expression levels were divided into quartiles. RESULTS: The p53 status of 372 patients' pathologic specimens was evaluated. In a subgroup of patients with p53-positive cancer (n = 226), 5-year RFS was 79% in the vitamin D group, which was significantly higher than the 57% in the placebo group (HR, 0.52; 95% confidence interval, 0.31-0.88; P = 0.02). In the subgroup of patients with p53-negative cancer, 5-year RFS in the vitamin D group versus placebo group was 72% versus 84% (not significantly different), respectively. Effect modification by p53 positivity was significant (P interaction = 0.02). However, no significant effect modification by either VDR or Ki-67 was observed. CONCLUSIONS: These results generate a hypothesis that vitamin D supplementation may improve RFS in patients with p53-positive digestive tract cancer. IMPACT: The results are still preliminary, but potentially important, because TP53 is the most frequently mutated gene across cancers at all sites.

Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial.

Some coauthors of this study previously performed the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative oral vitamin D supplementation (2,000 IU/day) in 417 patients with stage I to III digestive tract cancer from the esophagus to the rectum who underwent curative surgery (UMIN000001977). We conducted a post-hoc analysis of the AMATERASU trial to explore the effects of modification of vitamin D supplementation by histopathological characteristics on survival. Among patients with poorly differentiated adenocarcinoma, the 5-year relapse-free survival rate of patients supplemented with vitamin D was 91% compared with 63% in the placebo group (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08 to 0.78; P = 0.017; P for interaction = 0.023). Similarly, the 5-year overall survival rate was 92% in the vitamin D group compared with 72% in the placebo group (HR, 0.25; 95%CI, 0.07 to 0.94; P = 0.040; P for interaction = 0.012). In contrast, there were no significant effects in other histopathological characteristics between vitamin D and placebo groups. These findings generated the hypothesis that oral vitamin D supplementation may improve both relapse-free survival and overall survival in a subgroup of patients with poorly differentiated adenocarcinoma.

Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract Cancers: The AMATERASU Randomized Clinical Trial.

Importance: Randomized clinical trials of vitamin D supplementation for secondary prevention in patients with cancer are needed, given positive results of observational studies. Objective: To determine whether postoperative vitamin D3 supplementation can improve survival of patients with digestive tract cancers overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels. Design, Setting, and Participants: The AMATERASU trial, a randomized, double-blind, placebo-controlled trial conducted at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. Patients aged 30 to 90 years with cancers of the digestive tract from the esophagus to the rectum, stages I to III, were recruited. Of 439 eligible patients, 15 declined and 7 were excluded after operation. Interventions: Patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/d; n = 251) or placebo (n = 166) from the first postoperative outpatient visit to until the end of the trial. Main Outcomes and Measures: The primary outcome was relapse-free survival time to relapse or death. The secondary outcome was overall survival time to death due to any cause. Subgroups analyzed had baseline serum 25(OH)D levels of 0 to less than 20 ng/mL, 20 to 40 ng/mL, and greater than 40 ng/mL; because of small sample size for the highest-baseline-level group, interactions were tested only between the low- and middle-baseline-level groups. Results: All 417 randomized patients (mean age, 66 years; male, 66%; esophageal cancer, 10%; gastric cancer, 42%; colorectal cancer, 48%) were included in the analyses. There was 99.8% follow-up over a median 3.5 (interquartile range, 2.3-5.3) years, with maximal follow-up of 7.6 years. Relapse or death occurred in 50 patients (20%) randomized to vitamin D and 43 patients (26%) randomized to placebo. Death occurred in 37 (15%) in the vitamin D group and 25 (15%) in the placebo group. The 5-year relapse-free survival was 77% with vitamin D vs 69% with placebo (hazard ratio [HR] for relapse or death, 0.76; 95% CI, 0.50-1.14; P = .18). The 5-year overall survival in the vitamin D vs placebo groups was 82% vs 81% (HR for death, 0.95; 95% CI, 0.57-1.57; P = .83). In the subgroup of patients with baseline serum 25(OH)D levels between 20 and 40 ng/mL, the 5-year relapse-free survival was 85% with vitamin D vs 71% with placebo (HR for relapse or death, 0.46; 95% CI, 0.24-0.86; P = .02; P = .04 for interaction). Fractures occurred in 3 patients (1.3%) in the vitamin D group and 5 (3.4%) in the placebo group. Urinary stones occurred in 2 patients (0.9%) in the vitamin D group and 0 in the placebo group. Conclusions and Relevance: Among patients with digestive tract cancer, vitamin D supplementation, compared with placebo, did not result in significant improvement in relapse-free survival at 5 years. Trial Registration: UMIN Identifier: UMIN000001977.

Endoscopic submucosal dissection for the diagnosis and therapy of pedunculated gastric cancer with prolapse into the duodenal bulb: A case report.

INTRODUCTION: Preoperative diagnosis of gastric cancer invasion is not always sufficiently accurate. Diagnostic endoscopic submucosal dissection (ESD) can be performed for the purpose of accurate decision making and to avoid partial treatment vs aggressive over-treatment. We present a patient with the gastric cancer with indeterminate pre-operative diagnosis for depth of the invasion. CASE PRESENTATION: A 70-year-old man presented at our hospital because both anti-Helicobacter pylori (Hp) IGG antibody and serum pepsinogen (PG) levels were classified as positive. Upper gastrointestinal endoscopy was performed, and a large (3.5 cm) pedunculated polyp-shaped gastric cancer with prolapse into the duodenal bulb was found. [fluorine-18]-fluorodeoxy-glucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) imaging showed high 18F-FDG uptake, suggesting the possibility of advanced gastric cancer. Since the pre-operative diagnosis of the cancer invasion was indeterminable, diagnostic ESD was performed. The pathohistological diagnosis was early gastric cancer (33 × 35 × 20 mm, well differentiated tubular adenocarcinoma [tub1], pT1a[M], ly[--], v[--], UL[--], pHM0, pVM0) according to the Japanese classification of gastric carcinoma. DISCUSSION AND CONCLUSION: It was reported that ESD for early gastric cancers that met the expanded criteria was acceptable and should be the standard treatment instead of gastrectomy. The expanded criteria included cancer confined to the mucosa (cT1a), a single primary intestinal-type gastric adenocarcinoma, an ulcer-negative lesion of any size. We reported a case of pedunculated gastric cancer with prolapse into the duodenal bulb that could be treated by ESD. The present case is a good example of diagnostic ESD being used to minimize the damage of gastric cancer treatment.

New method of indocyanine green fluorescence sentinel node mapping for early gastric cancer.

BACKGROUND: The present study describes the retrospective feasibility study of ICG fluorescence SN mapping in back-table for early gastric cancer using PINPOINT®. METHOD: SN mapping were performed as following; the day before surgery, 0.5 ml ICG was injected endoscopically in four quadrants of the submucosa surrounding the gastric cancer using an endoscopic puncture. Intraoperatively, the gastrocolic ligament was divided to visualize all possible directions of lymphatic flow from the stomach. PINPOINT® (NOVADAQ, Canada) was used to illuminate regional lymph nodes from the serosal side. Positive staining was confirmed by at least 3 surgeons and an endoscopist during surgery (Figure 1). Lymph node dissection and gastrectomy were performed according to the criteria of gastric cancer treatment guidelines of JGCA. RESULT: All 6 patients had gastrectomy with laparoscopic approach. ICG positive lymphatic flow and lymph nodes were able to be observed in all the patients. Final pathological diagnosis was all StageI and curative resection. All the patients had ICG positive lymphatic area in left gastric artery (LGA) area. Two patients with tumor located in L area had ICG positive flow to right gastroepipoloic artery (RGEA) area. The mean of ICG positive lymph nodes was 8.6. One patient had a metastatic lymph node in station No.4, which was positive for ICG. CONCLUSION: Our method made identification of ICG positive lymph nodes easy in SN mapping in back-table under room light. Although further accumulation and analysis are necessary, we may be able to apply this method for intraoperative SN mapping of laparoscopic gastric cancer surgey.

Papillary thyroid carcinoma expressing CD20.

We identified a case of lymphadenopathy of metastatic papillary thyroid carcinoma (PTC) with CD20 expression, which was also expressed by the primary tumor. CD20 expression was identified using immunohistochemistry (IHC) in metastatic PTC biopsy samples from a 58-year-old woman. CD20 expression was initially determined using a CD20-recognizing L26 clone. To validate this phenomenon, we performed IHC with another antibody that recognizes the N-terminus of CD20 and fluorescent double staining using anti-TTF-1 and anti-CD20 antibodies. Taken together, we concluded metastatic PTC expressed CD20. We also examined 21 additional PTC cases and found four more cases that were CD20 positive. Therefore, five of the 22 (23%) cases were positive for CD20. In the positive cases, four cases were classical papillary thyroid carcinoma and one case was a follicular variant of papillary thyroid carcinoma. CD20 is an important target for molecularly targeted therapy for a subset of B-cell lymphomas. Complement-dependent and antibody-dependent cellular cytotoxicities are important effector mechanisms of anti-CD20 therapy. Here, for the first time, we report PTC with expression of CD20. Our findings provide a rationale for treating CD20-positive PTC patients with anti-CD20 therapy.

Thymoma with immunodeficiency/Good syndrome associated with myasthenia gravis.

Good syndrome is a rare condition in which thymoma is associated with hypogammaglobulinemia; it is characterized by repeated respiratory or systemic infections caused by bacteria, viruses, and fungi, as well as with various autoimmune disorders such as pure red cell aplasia. A 65-year-old woman was admitted to our hospital with ptosis and abdominal muscle weakness. Based on the presence of anti-acetylcholine receptor (Ach-R) antibodies, she was diagnosed with myasthenia gravis (MG). At that time, invasive thymoma of Masaoka stage IVa was also detected. Regression of thymoma and clinical remission of MG was achieved by chemotherapy followed by high-dose corticosteroid. However, several months later, the patient started developing repeated bacterial respiratory tract infections, cytomegalovirus infections, and esophageal and systemic candidiasis. Laboratory tests revealed a marked decrease of serum gamma-globulin levels (IgG 586 mg/dl, IgA 32 mg/dl, IgM 29 mg/dl) and severe reduction in the B cells ratio, as well as a decrease in the CD4+CD25+T cell to CD4+CD25-T cell ratio indicative of deregulation of CD4+T cell activation. These results suggested that the patient impaired humoral and cell-mediated immune responses. We continued the treatment with antibiotics and regular immunoglobulin supplementation through intravenous injections. Although autoimmune disorders are often observed in Good syndrome, the association with MG is quite rare. The case report is followed by the review of literature.