Right lateral approach to the superior mesenteric artery in robotic pancreaticoduodenectomy.

Ninomiya and colleagues introduced a novel approach to the superior mesenteric artery in robotic pancreaticoduodenectomy. The right lateral approach allows repositioning of the superior mesenteric artery to the right-most surface, facilitating safer artery division and simplifying detachment around the superior mesenteric vein, potentially reducing operative time and minimizing blood loss.

Predicting conversion surgery in patients with locally advanced pancreatic cancer after modified FOLFIRINOX treatment.

BACKGROUND: /Objective: FOLFIRINOX therapy (FFX) for locally advanced pancreatic cancer (LAPC) is increasingly recognized as a potent neoadjuvant therapy that enables transition to conversion surgery (CS). However, predictors of CS achievement after chemotherapy are controversial. This study aimed to demonstrate the efficacy of CS after modified FFX (mFFX) in patients with LAPC and to identify and score predictors of CS. METHODS: From January 2014 to December 2018, patients with LAPC who received mFFX as a first-line treatment were screened. Patients' overall survival was compared with and without CS. Moreover, the predictors for CS were analyzed to create scores for the CS factors. RESULTS: Forty-three patients received mFFX, including 20 patients who underwent CS (CS group, 46.5%). R0 resection was achieved in 16 patients (80%). The median survival time was 39.2 months (95% confidence interval [CI] 17.3-53.8) for the CS group and 16 months (95% CI 10.5-22.6) for the non-CS group (P < 0.001; hazard ratio 0.25, 95% CI 0.12-0.54). Since an average relative dose intensity of ≥90%, tumor reduction of ≥35%, and carbohydrate antigen 19-9 reduction of ≥70% or normalization were associated with successful transition to CS in the multivariate analysis, these factors were scored (CS score, range 0-3). All of the patients in the CS group fell into the 2-3 category, compared with 2 of 23 patients in the non-CS group (P < 0.001). CONCLUSION: CS after FFX contributes to the long-term survival of patients with LAPC. The CS score could be an indicator for transition to CS.

A patient with a pancreatic neuroendocrine tumor and multiple liver metastases achieved a long-term partial response to third-line streptozocin treatment.

The Japanese guideline for gastroenteropancreatic neuroendocrine tumor treatment recommends everolimus or sunitinib as first-line treatment for unresectable pancreatic neuroendocrine tumors (PNETs). Streptozocin (STZ) is recommended as an alternative. We encountered a patient with PNET who had multiple liver metastases and who showed a remarkable response to third-line STZ. The patient was a 50-year-old man with a pancreatic head tumor 32 mm in diameter. We planned to perform subtotal stomach-preserving pancreaticoduodenectomy, but abandoned resecting the pancreas during the surgery upon discovering a small liver tumor 3 mm in diameter, examination of frozen sections of which revealed a poorly differentiated adenocarcinoma. However, the final pathological examination revealed that the liver nodule was a PNET; hence, we completed the subtotal stomach-preserving pancreaticoduodenectomy 5 weeks after the first laparotomy. The patient received no adjuvant chemotherapy after surgery. Twenty-one months later, we discovered 20 scattered liver metastases via computed tomography; these were considered unresectable. Therefore, we administered everolimus for 7 months, but the patient developed interstitial pneumonia and experienced metastatic progression. Subsequent sunitinib administration for 6 months was ineffective. Finally, we chose STZ (1000 mg/m2, weekly) as a third-line treatment, which produced a partial response for 10 months. The patient remains alive 38 months after the detection of recurrence. As the order in which anti-cancer drugs should be administered to treat PNET has not been determined, additional predictors of their therapeutic efficacy should be investigated.

Successful resection of a granulocyte colony-stimulating factor-producing carcinoma of the pancreas: A case report.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation of precursor cells in the bone marrow and their maturation into fully differentiated neutrophils. G-CSF-producing cancers rarely occur in the digestive system, particularly the pancreas. Herein we report the rare case of a G-CSF-producing pancreatic carcinoma associated with severe anemia due to bleeding in the duodenum, which was successfully treated with surgery. A 79 year-old man presented with epigastralgia and anemia at our institution. Esophagogastroduodenoscopy revealed a duodenal tumor, which was diagnosed as a poorly differentiated adenocarcinoma. To control breeding, subtotal stomach-preserving pancreaticoduodenectomy was performed. The excised tumor measured 86×55×54 mm. It was primarily located in the pancreas and compressed the pancreatic parenchyma and main bile duct. It comprised poorly differentiated adenocarcinoma, and prominent neutrophil infiltration was noted around the tumor. Immunohistochemical examination revelaed that the tumor was positive for G-CSF expression. Based on these results, a final diagnosis of G-CSF-producing primary pancreatic cancer was made. At 18 months following surgery, the patient was alive without recurrence.

Laparoscopic fenestration for a large ruptured splenic cyst combined with an elevated serum carbohydrate antigen 19-9 level: a case report.

BACKGROUND: Non-parasitic splenic cysts are associated with elevated serum carbohydrate antigen (CA) 19-9 levels. We report a case in which a 23-year-old female exhibited a large ruptured splenic cyst and an elevated serum CA19-9 level. CASE PRESENTATION: The patient, who experienced postprandial abdominal pain and vomiting, was transferred to our hospital and was found to have a large splenic cyst during an abdominal computed tomography (CT) scan. On physical examination, her vital signs were stable, and she demonstrated rebound tenderness in the epigastric region. An abdominal CT scan revealed abdominal fluid and a low-density region (12 × 12 × 8 cm) with enhanced margins in the spleen. The patient's serum levels of CA19-9 and CA125 were elevated to 17,580 U/mL and 909 U/mL, respectively. A cytological examination of the ascitic fluid resulted in it being categorized as class II. Finally, we made a diagnosis of a ruptured splenic epidermoid cyst and performed laparoscopic splenic fenestration. The patient's postoperative course was uneventful, and she was discharged on postoperative day 5. The cystic lesion was histopathologically diagnosed as a true cyst, and the epithelial cells were positive for CA19-9. Follow-up laboratory tests performed at 4 postoperative months showed normal CA19-9 (24.6 U/L) and CA125 (26.8 U/L) levels. No recurrence of the splenic cyst was detected during the 6 months after surgery. CONCLUSION: Laparoscopic fenestration of a ruptured splenic cyst was performed to preserve the spleen, after the results of abdominal fluid cytology and MRI were negative for malignancy.

Pathomorphological features of metastatic lymph nodes as predictors of postoperative prognosis in pancreatic cancer.

To investigate the pathological features of metastatic lymph nodes (LN) in pancreatic ductal adenocarcinoma (PDAC) and to determine factors with prognostic implications.Metastatic LN status is a proven significant factor for predicting postoperative prognosis in pancreatic cancer patients. However, the effective prognostic criteria regarding metastatic LNs for such disease remain unknown.We retrospectively reviewed 98 patients with R0/1 resection for PDAC. All metastatic LNs were evaluated for the pathomorphological features of metastasis and analyzed in terms of postoperative outcomes. Various morphological patterns of metastasis were assessed in 440 positive LNs and then classified into 4 groups: common type, direct type (continuously invaded by the main tumor), scatter type (multiple tumor clusters among the normal LN tissues), and isolated tumor cell (ITC).The pathological stage was defined as stage IIA in 10% and IIB in 90% patients. Common-type metastasis was noted in 55% positive LNs of 75% node-positive patients; direct type in 36% LNs of 69% patients; scatter type in 5% LNs of 14% patients; and ITCs in 5% LNs of 18% patients. Significant difference was noted only in recurrence-free survival (RFS) but not in overall survival (OS) in the common-type; only in OS but not in RFS for the scatter type; and neither in RFS nor OS for both direct type and ITC. Multivariate analysis revealed that only LN ratio and curability were independent predictive factors of poor.The tumor distribution patterns in metastatic LNs are the postoperative prognostic factors in pancreatic cancer.

A case of intrahepatic cholangiocarcinoma that was difficult to diagnose prior to surgery: A case report.

The present study reports a case of mass-forming intrahepatic cholangiocarcinoma (ICC), which mimicked cholangiocellular carcinoma (CoCC) during imaging and a needle biopsy examination. A 51-year-old female with no relevant medical history was referred to the National Defense Medical College hospital with an intrahepatic tumor. Computed tomography demonstrated non-homogeneous enhancement in the early arterial phase and persistent enhancement in the portal and equilibrium phases, together with notable swelling of the para-aortic lymph nodes. Gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging revealed low signal intensity in the hepatobiliary phase. The liver tumor and lymph nodes exhibited increased radiotracer uptake (maximum standardized uptake value=14.0) with positron emission tomography. A histological examination of a percutaneous needle biopsy specimen of the liver tumor indicated a diagnosis of CoCC. The patient underwent left hepatectomy and lymphadenectomy. The surgical specimen contained a poorly differentiated adenocarcinoma with anaplastic changes, which was immunohistochemically positive for epithelial membrane antigen (at the luminal membrane), cytokeratins 7 and 19, and negative for α-fetoprotein, hepatocyte-specific antigen, cluster of differentiation 56 and KIT. Based on these histopathological and immunohistochemical findings, the patient was diagnosed with ICC.

Spin-Crossover Temperature Predictable from DFT Calculation for Iron(II) Complexes with 4-Substituted Pybox and Related Heteroaromatic Ligands.

Spin-crossover (SCO) is a reversible transition between low and high spin states by external stimuli such as heat. The SCO behavior and transition temperature (T 1/2) of a series of [FeII(X-pybox)2](ClO4)2 were studied to establish a methodology for ligand-field engineering, where X-pybox stands for 2,6-bis(oxazolin-2-yl)pyridine substituted with X at the 4-position of the pyridine ring. We utilized X = MeO, Me, 3-thienyl, Ph, H, MeS, 2-thienyl, N3, Cl, Br, 3-pyridyl, and 4-pyridyl. The solution susceptometry on five new derivatives with X = Me, 2-thienyl, N3, Br, and 3-pyridyl was performed in acetone, giving the SCO temperatures of 220, 260, 215, 280, and 270 K, respectively. The density-functional-theory molecular orbital (MO) calculation was performed on the ligands with geometry optimization. The atomic charge on the pyridine nitrogen atom [ρ(Npy)] was extracted from the natural orbital population analysis. Positive correlation appeared in the T 1/2 versus ρ(Npy) plot with R 2 = 0.734, being consistent with the analysis using the Hammett substituent constants (σp and σp +). This finding well agrees with the mechanism proposed: the rich electron density lifts the t2g energy level through the dπ-pπ interaction, resulting in a narrow t2g-eg energy gap and favoring the high-spin state and low T 1/2. The MO method was successfully applied to the known SCO-active iron(II) compounds involving 4-substituted 2,6-bis(pyrazol-1-yl)pyridines. A distinct positive correlation appeared in the T 1/2 versus ρ(Npy) plot. The comparison of correlation coefficients indicates that ρ(Npy) is a more reliable parameter than σp or σp + to predict a shift of T 1/2. Furthermore, this method can be more generalized by application to another known SCO family having 3-azinyl-4-p-tolyl-5-phenyl-1,2,4-triazole ligand series, where azinyl stands for a 2-azaaromatic ring. A good linear correlation was found in the T 1/2 versus ρ(NA) plot (NA is the ligating nitrogen atom in the azaaromatic ring). Finally, we will state a reason why the present treatment is competent to predict the SCO equilibrium position only by consideration on the electronic perturbation.

Intrahepatic Cholangiocarcinoma With Lymphoepithelioma-like Carcinoma Components Not Associated With Epstein-Barr Virus: Report of a Case.

A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as lymphoepithelioma-like carcinoma (LELC). Intrahepatic cholangiocarcinoma (ICC) with LELC components is rare, and most LELCs are associated with Epstein-Barr virus (EBV). We report here on a case of ICC with LELC components not associated with EBV. A 65-year-old woman was incidentally found to have a hepatic tumor in the caudate lobe. An extended right hepatectomy with lymphadenectomy was performed. Histologically, the tumor was mainly composed of large undifferentiated epithelial cells with vesicular nuclei, prominent nucleoli, indistinct cell borders, and heavy small lymphocytic infiltration, which are the characteristic features of LELC. Immunohistochemical studies revealed that the tumor cells were positive for cytokeratin 19 but were negative for glypican 3. In situ hybridization using EBV-encoded RNA was negative. Therefore, a diagnosis of ICC with LELC components not associated with EBV was made. Because there is limited information available regarding the prognosis and treatment of ICC with LELC components because of the limited number of reported cases, additional studies will be needed to clarify the clinicopathologic features of this disease.

Long great saphenous vein grafting as temporary coronary bypass for extended left hepatectomy: report of a case.

The right gastroepiploic artery (RGEA) has been used in coronary artery bypass grafting (CABG) as an alternative graft. In particular abdominal surgeries, surgery is required to rescue the graft flow into the coronary artery. A 77-year-old male with a history of CABG using RGEA was admitted with a diagnosis of a large hepatocellular carcinoma (HCC) occupying the whole caudate lobe. Preoperative coronary angiography indicated that the graft from the right internal mammary artery to the proximal left circumflex artery was obliterated among three branch bypasses. Following laparotomy, a great saphenous vein was harvested and delivered from the right axial artery to the RGEA graft over the thoracic wall, and the RGEA graft was ligated and divided. Subsequently, extended left hepatectomy was safely performed. Following hepatectomy, the RGEA graft was restored to the former condition, and the temporary graft was removed. After overcoming hyperbilirubinemia, the patient was discharged on postoperative day 28. This experience indicates that temporary bypass using the long great saphenous vein is effective and safe during long and invasive surgeries.

Acyl-CoA:cholesterol acyltransferase 1 mediates liver fibrosis by regulating free cholesterol accumulation in hepatic stellate cells.

BACKGROUND & AIMS: Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes the conversion of free cholesterol (FC) to cholesterol ester, which prevents excess accumulation of FC. We recently found that FC accumulation in hepatic stellate cells (HSCs) plays a role in progression of liver fibrosis, but the effect of ACAT1 on liver fibrosis has not been clarified. In this study, we aimed to define the role of ACAT1 in the pathogenesis of liver fibrosis. METHODS: ACAT1-deficient and wild-type mice, or Toll-like receptor 4 (TLR4)(-/-)ACAT1(+/+) and TLR4(-/-)ACAT1(-/-) mice were subjected to bile duct ligation (BDL) for 3 weeks or were given carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis. RESULTS: ACAT1 was the major isozyme in mice and human primary HSCs, and ACAT2 was the major isozyme in mouse primary hepatocytes and Kupffer cells. ACAT1 deficiency significantly exaggerated liver fibrosis in the mouse models of liver fibrosis, without affecting the degree of hepatocellular injury or liver inflammation, including hepatocyte apoptosis or Kupffer cell activation. ACAT1 deficiency significantly increased FC levels in HSCs, augmenting TLR4 protein and downregulating expression of transforming growth factor-ß (TGFß) pseudoreceptor Bambi (bone morphogenetic protein and activin membrane-bound inhibitor), leading to sensitization of HSCs to TGFß activation. Exacerbation of liver fibrosis by ACAT1 deficiency was dependent on FC accumulation-induced enhancement of TLR4 signaling. CONCLUSIONS: ACAT1 deficiency exaggerates liver fibrosis mainly through enhanced FC accumulation in HSCs. Regulation of ACAT1 activities in HSCs could be a target for treatment of liver fibrosis.

Multifocal lesions with pancreatic atrophy in IgG4-related autoimmune pancreatitis: report of a case.

We herein report a case of IgG4-related autoimmune pancreatitis (AIP). A 72-year-old male with jaundice visited our hospital complaining of epigastralgia. A blood chemistry analysis revealed elevated serum levels of total bilirubin and DUPAN-II. Computed tomography (CT) revealed irregularly shaped pancreatic masses with a stricture of the main pancreatic duct (MPD) in the head and tail that were interposed by marked atrophy with MPD dilation in the body. F-18 fluorodeoxyglucose (FDG)-positron emission tomography/CT revealed abnormally intense FDG uptake only at the masses. During surgery, another small tumor was also found in the atrophied body; therefore, a total pancreatectomy was performed under the diagnosis of multiple pancreatic cancers. The histological analysis revealed fibrosis with dense and diffuse infiltrations of lymphocytes and IgG4-positive plasma cells. The pancreatic parenchyma of the body was firmly replaced by fibrosis. AIP can lead to the formation of multiple pancreatic lesions, and thus the correct diagnosis is occasionally difficult to establish in atypical cases.

Removal of increased circulating CD4+CD25+Foxp3+ regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers.

BACKGROUND: Although sepsis-induced immunosuppression has long been considered to be a factor in the late mortality of patients with sepsis, little is known about regulatory T cell (Treg)-mediated immunosuppression and the effect of polymyxin B-immobilized fiber (PMX-F) on sepsis-induced immunosuppression. We sought to investigate the role of CD4(+)CD25(+)Foxp3(+) Tregs in septic patients, and to evaluate the effect of hemoperfusion with PMX-F on the recovery from immunosuppression owing to septic shock. METHODS: Thirty-two septic patients who had an identified focus of infection in the abdominal cavity were enrolled in this study. Peripheral blood mononuclear cells in the septic patients were examined to evaluate the roles of Tregs and the serum cytokine levels. We also examined the effects of PMX-F therapy on CD4(+) T cells, especially Tregs and serum cytokine levels in patients with septic shock. RESULTS: The percentage of Tregs in the CD4(+) T-cell population, and the serum IL-6 and IL-10 levels, were significantly higher among patients with septic shock compared with those without septic shock, and PMX-F therapy significantly decreased the number of Tregs, as well as the serum IL-6 and IL-10 levels. Furthermore, a significant increase in the number of CD4(+) T cells, a significant decrease in the percentage of Tregs in the CD4(+) T-cell population, and a significant decrease in the serum IL-6 and IL-10 levels 24 hours after PMX-F therapy were observed in septic shock survivors compared with nonsurvivors. CONCLUSION: We found a major increase in the percentage of Tregs in peripheral blood circulating CD4(+) T cells from patients with septic shock, and observed that the removal of Tregs by hemoperfusion with PMX-F might represent a novel strategy for inducing recovery from the immunosuppression associated with sepsis.

Importance of maintaining left gastric arterial flow at Appleby operation preserving whole stomach for central pancreatic cancer.

The safety of whole stomach-preserving Appleby operation with resection of the left gastric artery (LGA) for pancreatic cancer cannot be assured. The anatomy of the celiac axis (CA) with special regard to the position of the origin of the LGA was examined. Using 3D images of the vascular architecture reconstructed from volume data of helical CT, the length of the CA and the position of the origin of the LGA from the CA were measured in 53 patients. Among 53 patients, 47 patients (89%) had classical anatomy of the CA branches. The mean length(2 standard deviation) of the CA and the distance from the root of the LGA to the bifurcation of the CA were 25.2mm (-4.9) (range 14.6-36.5) and 10.3mm (+4.5)(range 2.4-21.9), respectively. In 23 (45%) cases, the LGA arose farther than 10mm away from the bifurcation of the CA. Among six patients with anatomical variation of the arteries, two (4%) had the LGA directly arising from the aorta. Conservation of the LGA at modified Appleby operation would give complete cancer removal by en bloc resection of the nerve plexus, without risk of ischemic complications of the stomach and liver.

The postoperative serum interleukin-15 concentration correlates with organ dysfunction and the prognosis of septic patients following emergency gastrointestinal surgery.

OBJECTIVE: To clarify the time course of changes in the serum interleukin-15 (IL-15) concentrations in septic patients undergoing emergency surgery for abdominal infection and to investigate whether the serum IL-15 levels correlate with the postoperative clinical course of septic patients. METHODS: Twenty-four septic patients who had intra-abdominal infection and who underwent an emergency operation were enrolled in this study. The serum IL-15 levels were measured before surgery, and on postoperative d 1 (POD1), POD3, and POD5, and the relationship between the serum IL-15 levels and the postoperative clinical course estimated by the Systemic Inflammatory Response Syndrome (SIRS) criteria, Acute Physiology and Chronic Health Evaluation (APACHE-II) score, the parameters of organ function, and the 30-d mortality were evaluated. RESULTS: The time course of changes of the serum IL-15 levels were significantly different between survivors and non-survivors (P < 0.05, by repeated measures analysis of variance [ANOVA]). There was a statistically significant relationship between the serum IL-15 levels on POD1 or POD3 and the duration of SIRS (R = 0.50, P < 0.05, R = 0.65, P < 0.01, respectively). Furthermore, a significant positive correlation was observed between the serum IL-15 levels on POD1 and the creatinine levels on POD1 or POD3 (R = 0.48, P < 0.05, R = 0.50, P < 0.05, respectively), and a significant negative correlation between the serum IL-15 levels on POD1 or POD 3 and the PaO(2)/FiO(2) on POD3 (R = -0.51, P < 0.05, R = -0.69, P < 0.01, respectively). CONCLUSIONS: The measurement of postoperative serum level of IL-15 might be useful for predicting the severity of SIRS and organ dysfunction, especially renal and pulmonary dysfunction.

Postoperative serum concentrations of high mobility group box chromosomal protein-1 correlates to the duration of SIRS and pulmonary dysfunction following gastrointestinal surgery.

OBJECTIVE: To clarify the time course of changes in the serum HMGB-1 concentrations in patients undergoing major gastrointestinal surgery, and to investigate whether the serum HMGB-1 levels correlate with the postoperative clinical course of the patients. METHODS: Twenty-eight patients with alimentary tract carcinoma who underwent elective gastrointestinal surgery were enrolled in this study. The correlation between the serum HMGB-1 levels and the postoperative clinical course were evaluated. RESULTS: Serum HMGB-1 concentrations in patients who underwent surgery for gastrointestinal cancer increased gradually during postoperative days, and reached peak concentrations on postoperative day 3 (POD3). There was a statistically significant positive correlation between the serum HMGB-1 levels on POD3 or POD5 and the duration of SIRS (r = 0.68, P < 0.001, r = 0.45, P < 0.05, respectively). A significantly positive correlation was found between the serum HMGB-1 levels on POD3 or POD5 and the heart rates on POD3 or POD5. Furthermore, there was a negative correlation between the serum HMGB-1 levels and PaO2/FiO2 ratio on POD3. CONCLUSIONS: Serum HMGB-1 levels increase after major gastrointestinal surgery, and the serum peak HMGB-1 levels correlate with the duration of SIRS and postoperative pulmonary dysfunction.

Oral administration of the thrombin receptor antagonist E5555 (atopaxar) attenuates intimal thickening following balloon injury in rats.

Thrombin is a powerful agonist for a variety of cellular responses including platelet aggregation and vascular smooth muscle cell (SMC) proliferation. These actions are mediated by a thrombin receptor known as protease-activated receptor-1 (PAR-1). Recently we discovered that 1-(3-tert-butyl-4-methoxy-5-morpholinophenyl)-2-(5,6-diethoxy-7-fluoro-1-imino-1,3-dihydro-2H-isoindol-2-yl)ethanone hydrobromide (E5555, atopaxar) is a potent and selective thrombin receptor antagonist. This study characterized the pharmacological effects of E5555 on SMC proliferation in vitro and in a rat model of intimal thickening after balloon injury in vivo. E5555 selectively inhibited rat aortic SMC proliferation induced by thrombin and thrombin receptor-activating peptide (TRAP) with half maximal inhibitory concentration (IC(50)) values of 0.16 and 0.038 µM, respectively. E5555 did not inhibit rat SMC proliferation induced by basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) at concentrations up to 1µM. In addition, E5555 inhibited human aortic SMC proliferation induced by thrombin at concentrations of 0.3 and 3units/ml with IC(50) values of 0.028 and 0.079 µM, respectively, whereas it did not affect bFGF-induced proliferation at concentrations up to 1µM. Repeated oral administration of 30 mg/kg E5555 (once daily for 16 days) significantly reduced neointimal formation in the balloon-injured rat arterial model. These results suggested that a PAR-1 antagonist could be effective for treating restenosis following vascular intervention in addition to preventing thrombus formation. E5555 could thus have therapeutic potential for restenosis and chronic atherothrombotic disease.

Copper(I)-catalyzed substitution reactions of propargylic amines: importance of C(sp)-C(sp3) bond cleavage in generation of iminium intermediates.

Substitution reactions of propargylic amines proceed in the presence of copper(I) catalysts. Mechanistic studies showed that C(sp)-C(sp(3)) bond cleavage assisted by nitrogen lone-pair electrons is essential for the reaction, and the resulting iminium intermediates undergo amine exchange, aldehyde exchange, and alkyne addition reactions. Because iminium intermediates are key to aldehyde-alkyne-amine (A(3)) coupling reactions, this transformation is effective not only for reconstruction of propargylic amines but also for chiral induction of racemic compounds in the presence of chiral catalysts.

Poorly differentiated adenocarcinoma with signet-ring cell carcinoma of the extrahepatic bile duct in a 42-year-old Japanese female: a case report.

Poorly differentiated adenocarcinoma without papilla or tubule formation of the extrahepatic bile duct is rare. Here we present a case (a 42-year-old Japanese woman) without either pancreatobiliary maljunction or liver disease. The patient had obstructive jaundice. Imaging studies revealed a bile duct tumor obstructing the common bile duct and invading the surrounding tissues. Pathologic examination revealed a dense periductal growth of poorly differentiated adenocarcinoma containing signet-ring cells, but without papilla or tubule formation in the extrahepatic bile duct. The tumor cells directly invaded the pancreatic parenchyma and the portal vein. In the extrahepatic bile duct, poorly differentiated adenocarcinoma may be established as a distinct clinicopathologic entity if the tumors are characterized by: 1) the absence of papilla or tubule formation, 2) Asian preponderance, 3) occurrence at a younger age than is usual for patients with biliary cancers, and 4) an aggressive mural invasiveness.