Clinical impacts of positive intraepithelial neoplasia at pancreatic transection margin in pancreatic cancer surgery.

BACKGROUND/OBJECTIVES: The outcomes of patients with intraepithelial neoplasia at the pancreatic transection margin after pancreatic cancer surgery remain unclear. We evaluated the clinical impact of pancreatic transection margin status. METHODS: This retrospective observational study included 171 patients who underwent surgery for pancreatic ductal adenocarcinoma between January 2008 and December 2019. Patients were classified into three groups: negative pancreatic transection margin (group N), positive low-grade (group L), and positive high-grade (group H) intraepithelial neoplasia. The clinicopathological findings and prognoses were analyzed for each group. RESULTS: There were 140, 14, and 9 patients in groups N, L, and H, respectively. The median age was significantly higher in group H (p = 0.035). There were no significant differences in male ratio, preoperative chemotherapy administration rate, pretreatment tumor markers, operative procedure, operative time, or blood loss. Overall survival and recurrence-free survival were not significantly different; however, the cumulative risk of recurrence in the remnant pancreas was significantly higher in group H (p = 0.018). CONCLUSIONS: Intraepithelial neoplasia at the pancreatic transection margin did not affect overall/recurrence-free survival. As patients with high-grade intraepithelial neoplasia at the pancreatic transection margin have an increased risk of recurrence in the remnant pancreas, careful postoperative follow-up is required.

Cilostazol improves the prognosis after hepatectomy in rats with sinusoidal obstruction syndrome.

BACKGROUND AND AIM: Safe radical hepatectomy is important for patients with colorectal liver metastases complicated by sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy. This study aimed to investigate the impact of preoperative administration of cilostazol (CZ), an oral selective phosphodiesterase III inhibitor, on hepatectomy in rat SOS model. MATERIAL AND METHODS: Rats were divided into NL (normal liver), SOS (monocrotaline [MCT]-treated), and SOS + CZ (MCT + CZ-treated) groups. MCT or CZ was administered orally, and a 30% partial hepatectomy was performed 48 h after MCT administration. Postoperative survival rates were evaluated (n = 9, for each). Other rats were sacrificed on postoperative days (POD) 1 and 3 and evaluated histologically, immunohistochemically, biochemically, and using transmission electron microscopy (TEM), focusing particularly on SOS findings, liver damage, and liver sinusoidal endothelial cell (LSEC) injury. RESULTS: The cumulative 10-day postoperative survival rate was significantly higher in the SOS + CZ group than in the SOS group (88.9% vs 33.3%, P = 0.001). Total SOS scores were significantly lower in the SOS + CZ group than in the SOS group on both POD 1 and 3. Serum biochemistry and immunohistochemistry showed that CZ reduced liver damage after hepatectomy. TEM revealed that LSECs were significantly preserved morphologically in the SOS + CZ group than in the SOS group on POD 1 (86.1 ± 8.2% vs 63.8 ± 9.3%, P = 0.003). CONCLUSION: Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS.

[A Case of Rectal Cancer with Virchow Lymph Node Metastasis in Which Complete Response Was Achieved with Chemoradiation Therapy].

A 43-year-old man underwent a low anterior resection of the rectum due to upper rectal cancer. The pathological Stage was Ⅳ with para-aortic lymph node metastasis. Postoperative chemotherapy with CapeOX was initiated, but para-aortic lymph node metastasis was discovered 4months after the surgery. Chemoradiation therapy with Cape and Bev, and 70 Gy/28 Fr led to the disappearance of the metastasized lesions. At 13months after the surgery, FDG accumulation was observed in the Virchow's lymph node, and chemotherapy with IRIS and Bev was initially administered. Subsequently, chemoradiation therapy with S-1 and Bev, and 66 Gy/33Fr was administered, followed by chemotherapy with S-1 and Bev, S-1. These therapies led to complete response(CR). However, 35 months after the surgery, the Virchow's lymph node had enlarged again, and chemoradiation therapy with S-1 and 60 Gy/30Fr was administered. Although no FDG accumulation was detected in the lymph node at 40 months after the surgery, metastasis was found in the mediastinal lymph nodes. Panitumumab therapy achieved CR, and no metastasis had been identified at 60 months after the final therapy. Chemoradiation therapy is a treatment option to improve the prognosis of patients with metastasis only in the Virchow's lymph node.

Clinicopathological features of cholangiolocarcinoma and impact of tumor heterogeneity on prognosis: A single institution retrospective study.

Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor.

Early progression of a pancreatic metastasis of synovial sarcoma after pancreatectomy.

BACKGROUND: Synovial sarcoma is a malignant tumor that constitutes up to 10% of all soft-tissue sarcomas. The most frequent metastatic sites of synovial sarcoma are the lungs, lymph nodes, and bone, whereas pancreatic metastasis is extremely rare. Here, we report a case of pancreatic metastasis of synovial sarcoma. CASE PRESENTATION: Nine years before presentation, a 31-year-old woman underwent extensive resection of the primary tumor after chemotherapy for left upper extremity synovial sarcoma. Six months before presentation, interscapulothoracic amputation was performed for an enlarged mass in the left upper extremity; the patient was treated with pazopanib. Three months before presentation, chest computed tomography showed multiple lung metastases; during subsequent follow-up, abdominal computed tomography revealed a pancreatic metastasis of synovial sarcoma. The doubling time of the pancreatic tumor was 14 days, and it grew rapidly. Furthermore, treatment-resistant pancreatitis symptoms were detected; thus, we performed distal pancreatectomy and administered one course of a 70% dose of trabectedin. However, the patient died of rapid progression of lung metastasis and respiratory failure within 2 months after surgery. CONCLUSIONS: Pancreatectomy may be carefully performed in cases of isolated pancreatic metastasis. However, the presence of other distant extrapancreatic metastases (e.g., uncontrolled lung metastases) may rule out pancreatectomy treatment.

Hemophagocytic Lymphohistiocytosis With Elevated Cytokines Related to Macrophage Activation After Liver Transplantation for Autoimmune Hepatitis: A Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal complication of liver transplantation (LT). HLH is characterized by pathologic macrophage activation with hypercytokinemia, excessive inflammation, and tissue destruction, resulting in progressive organ dysfunction. HLH is also known as macrophage activation syndrome (MAS) when complicated by rheumatic or autoinflammatory diseases. Measuring several serum cytokines could be helpful in diagnosing HLH and MAS. Cytokines related to macrophage activation: neopterin, interleukin-18 (IL-18), and soluble tumor necrosis factor receptors (sTNF-R) I and II have not been assessed in patients with HLH complicated by LT. In this case, these cytokines were evaluated in the perioperative period of LT. The patient was a 24-year-old woman who underwent living-donor LT for acute worsening of autoimmune hepatitis. On postoperative day 12, the patient was diagnosed with HLH on the basis of the criteria. Plasma exchange, steroid pulse therapy, intravenous immunoglobulin and granulocyte-colony stimulating factor effectively inhibited progression to lethal HLH. When HLH occurred after LT, cytokine analysis showed that neopterin, IL-18, sTNFR-I, and II were elevated: cytokine storm. Of note, cytokine analysis on hospital admission also revealed elevated cytokine levels. Particularly, IL-18 levels were markedly elevated, suggesting that activation of the innate immune system was involved. These results revealed that a cytokine storm and macrophage activation developed before LT. Based on these findings, cytokine analysis related to macrophage activation may be useful for diagnosing and predicting HLH and MAS in patients with LT.

Case of resected small-cell neuroendocrine carcinoma of the extrahepatic bile duct.

Neuroendocrine carcinomas (NECs) arising from the extrahepatic bile duct (EHBD) are extremely rare, and their preoperative diagnosis is difficult. A small number of resected cases of EHBD NECs has been reported, and their prognosis is usually poor. A 62-year-old man presented with obstructive jaundice and liver disease. Radiological imaging revealed wall thickness and stricture of the distal common bile duct (CBD); however, lymph node or distant metastasis was not detected. Adenocarcinoma was detected on biopsy, and surgery was performed with a preoperative diagnosis of cholangiocarcinoma of the distal CBD. Pathological examination revealed adenocarcinoma of the CBD mucosa (20%) and NEC of the CBD wall (80%). The final pathological diagnosis was small-cell NEC of the EHBD. His post-operative course was good, and there was no recurrence for 4 months after surgery. Herein, we report a case of resected EHBD NEC and a literature review.

Acute acalculous cholecystitis caused by gallbladder metastasis due to the peritoneal dissemination of gastric cancer: A case report.

INTRODUCTION AND IMPORTANCE: Acute acalculous cholecystitis (AAC) is associated with a high mortality rate. AAC caused by metastasis to the gallbladder is rare. We report a case of AAC caused by gallbladder metastasis due to the peritoneal dissemination of gastric cancer. CASE PRESENTATION: An 84-year-old male visited our hospital because of epigastric pain. Ultrasonography and computed tomography revealed swelling and thickening of the gallbladder wall, but stones were not observed in the gallbladder. We performed emergency surgery with a diagnosis of acute cholecystitis. Laparoscopy revealed the presence of many nodules around the abdominal cavity including the hepatoduodenal ligament. Inflammation of Calot's triangle was severe, so we performed subtotal cholecystectomy. We also resected one of the peritoneal nodules. Macroscopically, there were no stones in the gallbladder and histopathological examination revealed acute cholecystitis and existence of adenocarcinoma involving the subserosa of the gallbladder wall and the resected peritoneal nodule. After surgery, esophagogastroduodenoscopy revealed Borrmann type II lesions at the antrum and gastric biopsy showed adenocarcinoma. He was diagnosed with advanced gastric cancer with peritoneal dissemination. His postoperative course was good. CLINICAL DISCUSSION: The cases of AAC caused by gallbladder metastasis have been little reported in the literature. This case is advanced gastric cancer with peritoneal dissemination and AAC was thought to be caused by peritoneal dissemination from operative and histopathological findings. We successfully treated this rare case of AAC with laparoscopic surgery. CONCLUSION: Although metastasis to the gallbladder is rare, it is necessary to be aware of this possibility when treating AAC.

Successful treatment of a right internal mammary artery aneurysm with thoracoscopic surgery.

Internal mammary artery aneurysms are rarely detected, with only a few cases caused by physical trauma, connective tissue diseases, and vasculitis having been reported. We describe the case of a 52-year-old woman diagnosed with a right internal mammary artery aneurysm several months after experiencing a DeBakey Ⅲ acute aortic dissection. The artery had an indication of dissection that seemed to have caused the aneurysm. Thoracoscopic resection was performed, and the patient recovered with no major complications.

Solitary choroidal metastasis from gastric adenocarcinoma: a case report.

BACKGROUND: Metastatic choroidal carcinomas that originated from the gastrointestinal tract are extremely rare. We report a case of suspected solitary choroidal metastasis from gastric adenocarcinoma. CASE PRESENTATION: The patient was a 60-year-old man who had undergone laparoscopic distal gastrectomy with D1+ lymphadenecetomy for gastric cancer. The clinical stage was T1bN0M0 (TNM classification), but the pathological stage was T4aN0M0 beyond expectation. Adjuvant chemotherapy with oral Tegafur, Gimeracil, Oteracil potassium (TS-1®) was initiated. But he suddenly complained of decreased visual acuity in his right eye about 8 months later. This was suspected to be caused by choroidal metastasis of gastric adenocarcinoma. Chemotherapy with paclitaxel (PTX) and intensity-modulated radiotherapy (IMRT) achieved complete remission and spared the patient from going blind. CONCLUSIONS: This case demonstrates that we should be aware of the possibility of choroidal metastases, when visual symptoms arise during treatment of gastric cancer.

Clinical significance of a false lumen pathway through the arch in acute type A aortic dissection and its influence on cervical branch compromise.

OBJECTIVES: Upon onset of acute type A aortic dissection, the aortic true lumen generally becomes fixed around the supra-aortic branches in the greater curvature and Botallo's ligament in the lesser curvature of the aortic arch. Therefore, the pathways of the false lumen through the arch can be categorized as anterior, bilateral and posterior. We investigated the relationship between a false lumen pathway through the arch and cervical branch compromise, stratified by primary tear location. METHODS: Sixty-four consecutive patients with acute type A aortic dissection underwent emergency surgery at our institution between March 2005 and October 2013. Of these, 40 cases (63%) were DeBakey type I, 15 cases (23%) were type II and 9 cases (14%) were type III-D (retrograde type A). We conducted a retrospective review of preoperative computed tomographic angiography using three-dimensional image post-processing tools for 43 cases, excluding 15 cases with type II and 6 cases with type I for which preoperative digital image data were not available. RESULTS: Of the 43 cases, 14, 18 and 11 revealed anterior, bilateral and posterior pathways, respectively. Twenty-one cases (49%) showed a primary intimal tear in the ascending aorta (8 anterior, 12 bilateral and 1 posterior), 12 cases (28%) showed a primary intimal tear in the aortic arch (5 anterior, 3 bilateral and 4 posterior) and 10 cases (23%) showed a primary intimal tear in the descending aorta (1 anterior, 3 bilateral and 6 posterior). Twelve of the 14 anterior pathway cases (86%) had a total of 26 supra-aortic branch compromises, 13 of the 18 bilateral pathway cases (72%) had a total of 20 supra-aortic branch compromises, while only 4 of the 11 posterior pathway cases (36%) had a total of four supra-aortic branch compromises. None of the 11 posterior pathway cases had a dissection extending into all 3 supra-aortic branches. CONCLUSIONS: Posterior pathway cases generally showed primary tear locations in the arch or descending aorta, and cervical branch compromise was rare. Aortic dissections tended to extend into the cervical branches through the anterior side of the aortic arch. A false lumen pathway through the arch was strongly associated with cervical branch compromise in acute type A aortic dissections.

Morphological Characterization of First Instar Larvae of Asian Horseshoe Crabs and their Hybrids*: (horseshoe crabs/interspecific hybrids/larvae).

The morphological characters of first instar larvae of three Asian horseshoe crabs and their hybrids were examined. For this purpose, the length of six parts on the larvae, the pattern of pigmentation, the structure of the margin of the opisthosoma, and the distribution and shape of spines on the extracardiac region of the prosoma were recorded. In general, the phenotypes of the hybrids were intermediate between those of the parents, suggesting that both male and female genomes contribute to development of the hybrids. However, there were some exceptional characters and phenotypic variations. Some characters were inherited from only one parent. This was suggested to imply that if the maternal species did not have the gene regulating expression of a given paternal character, the paternal gene did not express this character.

THE DEVELOPMENTAL APPEARANCE OF PATERNAL FORMS OF LACTATE DEHYDROGENASE AND MALATE DEHYDROGENASE IN HYBRID HORSESHOE CRABS.

Differences in electrophoretic mobilities of lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) existed between three Asian horseshoe crabs, Tachypleus tridentatus, Tachypleus gigas, and Carcinoscorpius rotundicauda, used for interspecific hybridization. After electrophoresis of extracts of hybrid horseshoe crab embryos on starch gels, the paternal, maternal, and hybrid forms of the LDH and MDH were detected with specific enzyme staining. In viable hybrids the paternal form of the LDH was detected at stage 17 (immediately before the 1st embryonic molt). Similarly, evidence of gene expression for mitochondrial MDH was seen at stage 14 (stage of appearance of rudimental appendages). Gene expression for supernatant MDH was seen at stage 17 (immediately before the 1st embryonic molt). Regarding the onset of genome control in embryogenesis, it was suggested that prior to the activation of the maternal gene of the LDH, the paternal gene of the LDH was activated in horseshoe crab hybrids. Furthermore, there was evidence that the maternal effects on early embryogenesis were due to enzymes present in the egg prior to fertilization, not to continued synthesis directed by stable messenger RNA.

A SPECIATIONAL HISTORY OF "LIVING FOSSILS": MOLECULAR EVOLUTIONARY PATTERNS IN HORSESHOE CRABS.

Horseshoe crabs' exceptional morphological conservatism over the past 150 My has led to their reputation as "living fossils," but also has served to obscure phylogenetic relationships within the complex. Here we employ nucleotide sequences from two mitochondrial genes to assess molecular evolutionary rates and patterns among all extant horseshoe crab species. The American species Limulus polyphemus proved to be the sister taxon to a clade composed of the Asiatic species Tachypleus gigas, T. tridentatus, and Carcinoscorpius rotundicauda, whose relationships inter se were not resolved definitively. Both absolute and relative rate tests suggest a moderate slowdown in sequence evolution in horseshoe crabs. Nonetheless, dates of the lineage separations remain uncertain primarily because of reservations about molecular-clock calibrations resulting from large rate variances at examined loci across Arthropods and other animal lineages, as inferred in this and prior studies. Thus, ironically, separation dates as estimated by molecular evidence in general may remain most insecure in taxonomic groups for which such information is needed most-those lacking strong biogeographic or fossil benchmarks for internal-clock calibrations. In any event, the current results show that large numbers of molecular characters distinguish even these most morphologically conservative of organisms. Furthermore, comparisons against previously published mitochondrial sequence data in the morphologically dynamic hermit crab-king crab complex demonstrates that striking heterogeneity in levels of morphotypic differentiation can characterize Arthropod lineages at similar magnitudes of molecular divergence.