Visible-light-driven 1,2-hydro(cyanomethylation) of alkenes with chloroacetonitrile.

A regioselective 1,2-hydro(cyanomethylation) of unactivated aliphatic alkenes is reported. A cyanomethyl radical is generated from haloacetonitriles. This radical adds onto alkenes to form alkyl radicals, which undergo hydrogen atom transfer from thiol to produce one-carbon-extended nitriles. Furthermore, the alkyl radicals are applied to cascade cyclization.

Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management.

Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs.

Isolated metastases to the common iliac and mesorectal lymph nodes suggesting an atypical metastatic route in upper rectal cancer: A case report.

INTRODUCTION: Most lymphatic vessels in the upper rectum run parallel to the superior rectal artery and up to the inferior mesenteric artery. Here, we report a rare case of upper rectal cancer with atypical lymphatic spread. PRESENTATION OF CASE: A 39-year-old woman was diagnosed with upper rectal cancer and isolated lymph node (LN) metastases to the mesorectal and right common iliac LNs. The patient underwent laparoscopic low anterior resection with targeted dissection of the right common iliac LNs. The pathological diagnosis was T3N2M0, and the patient received postoperative adjuvant chemotherapy. One year later, local recurrence was found at the sacral promontory level, where the targeted lymphadenectomy had been performed previously. The recurrent tumor was surgically resected together with the attached presacral fascia. The patient subsequently received postoperative adjuvant chemotherapy, and there was no recurrence one year after the last surgery. DISCUSSION: Isolated metastases were observed in the right common iliac and mesorectal LNs. The locally recurrent tumor included lymphatic vessels running along the median sacral artery. No metastatic tumor was found in the internal iliac area at the time of the initial diagnosis nor during recurrence. Thus, this case suggests the presence of a rare metastatic route from the mesorectal LN to the common iliac LN via the median sacral lymphatics. CONCLUSION: Lymphatic spread of rectal cancer may be predictable; however, rare patterns of LN metastasis can exist. The assessment of lymphatic flow is crucial for improving the oncological outcomes of rectal cancer surgery.

Ligand-Controlled Regiodivergence in Nickel-Catalyzed Vinylcyclopropane Rearrangement.

A ligand-controlled regiodivergence in Ni-catalyzed rearrangement of vinylcyclopropanes to 1,4- or 1,5-disubstituted cyclopentenes is reported. The 1,4- or 1,5-disubstituted cyclopentene is selectively obtained depending on the choice of ligands. Detailed kinetic studies and density functional theory calculations on the catalytic cycle revealed that the product selectivity is determined at the reductive elimination step from the six-membered η1 -allyl intermediate.

[A Case of Hepatic Undifferentiated Embryonal Sarcoma in an Adult].

A 20-year-old woman was admitted with abdominal pain and a cystic liver tumor. A hemorrhagic cyst was suspected. Contrast-enhanced computed tomography(CT)and magnetic resonance imaging(MRI)revealed a space-occupying solid mass in the right lobule. Positron emission tomography(PET)-CT revealed 18F-fluorodeoxyglucose uptake in the tumor. We performed a right hepatic lobectomy. Histopathological evaluation of the resected tumor revealed an undifferentiated embryonal sarcoma of the liver(UESL). The patient refused adjuvant chemotherapy but showed no recurrence 30 months postoperatively. UESL is a rare malignant mesenchymal tumor that occurs in infants and children. It is extremely rare and is associated with poor prognosis in adults. In this report, we described a case of adult UESL.

Cu-Catalyzed Double C(sp3)-H Functionalization of Ethylarenes to Form Arylethanolamines.

A double C(sp3)-H functionalization of ethylarenes with alcohols and N-fluorobenzenesulfonimide is reported. The reaction proceeds in three stages. (1) Cu-catalyzed benzylic alkoxylation of ethylarenes gives 1-(1-alkoxyethyl)benzenes. (2) The resulting 1-(1-alkoxyethyl)benzenes are gradually converted into vinylarenes. (3) Cu-catalyzed aminoalkoxylation of the intermediary vinylarenes yields arylethanolamines. Overall, the C-N and C-O bonds are introduced regioselectively at the homobenzylic and benzylic positions of ethylarenes.

Diagnosis, Treatment, and Prevention of Ileostomy Complications: An Updated Review.

An ileostomy is associated with multiple complications that may frequently or persistently affect the life of ostomates. All healthcare professionals should have knowledge of the diagnosis, treatment, and prevention of ileostomy complications. Peristomal dermatitis is caused by watery and highly alkaline effluent. Skin protective products are typically used for local treatment. Ischemia/necrosis occurs due to insufficient arterial blood supply. Retraction is seen in patients with a bulky mesentery and occurs following ischemia. Convex stoma appliances can be used for skin protection against fecal leakage. Small bowel obstruction (SBO) is common and occurs only at the stoma site. Trans-stomal decompression is most effective in these cases. High output stoma (HOS) is defined as a condition when the output exceeds 1,000- 2,000 ml/day, lasting for one to three days. Treatment includes intravenous fluid and electrolyte resuscitation followed by restriction of hypotonic fluid and the use of antimotility (and antisecretory) drugs. Stomal prolapse is a full-thickness protrusion of an inverted bowel. Manual reduction is attempted initially, whereas emergency bowel resection may be needed for incarcerated cases. A parastomal hernia (PSH) is an incisional hernia of the stoma site. Surgery is considered in cases of incarceration, but most cases are manageable with non-surgical treatment.

Oncologic impact of colonic stents for obstructive left-sided colon cancer.

Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer (OLCC) in terms of both palliative treatment and bridge-to-surgery (BTS). Notably, many studies have convincingly demonstrated the effectiveness of stenting as a BTS, resulting in improvements in short-term outcomes and quality of life, safety, and efficacy in subsequent curative surgery, and increased cost-effectiveness, whereas the safety of chemotherapy after stenting and the long-term outcomes of stenting as a BTS are controversial. Several studies have suggested an increased risk of perforation in patients receiving bevacizumab chemotherapy after colonic stenting. In addition, several pathological analyses have suggested a negative oncological impact of colonic stenting. In contrast, many recent studies have demonstrated that colonic stenting for OLCC does not negatively impact the safety of chemotherapy or long-term oncological outcomes. The updated version of the European Society of Gastrointestinal Endoscopy guidelines released in 2020 included colonic stenting as a BTS for OLCC as a recommended treatment. It should be noted that the experience of endoscopists is involved in determining technical and clinical success rates and possibly oncological outcomes. This review discusses the positive and negative impacts of colonic stenting on OLCC treatment, particularly in terms of oncology.

Major basic protein deposited at intra mucosal epithelium with probable eosinophilic chronic rhinosinusitis.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is diagnosed by Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system and histopathological eosinophil counts of dissected nasal polyps. Patients with low JESREC score and small number of tissue eosinophils are diagnosed with non-ECRS (NECRS). Due to the 2 parameters of this diagnostic system, chronic rhinosinusitis is to be divided to 4 groups and some patients fall into the 2 groups other than ECRS and NECRS: probable ECRS (pECRS) and probable non-ECRS (pNECRS). We attempted to clarify clinical and histopathological similarities and differences, especially concerning major basic protein (MBP), among those groups. Methods: One hundred twenty-eight patients treated by endoscopic sinus surgery was included. Clinical characteristics were compared among each group, and immunohistological analysis for MBP was performed to 35 randomly selected patients. MBP deposition at intra mucosal epithelium was evaluated by semiquantificational approach. Results: ECRS patients showed significantly higher comorbidity rate with allergic rhinitis (36 patients, 78.3%), asthma (36 patients, 78.3%) compared with other groups. Also, percentage of the patients complaining olfactory dysfunction (42 patients, 91.3%) was significantly higher (p < 0.001). Lund-Mackay score (mean, 14.5; 6-24) and recurrence rate (27 patients, 61.4%) was the highest in ECRS patients. Regarding pECRS, the number of patients with olfactory dysfunction (5 patients, 55.6%) was higher than pNECRS and NECRS groups. Also, comorbidity of asthma and percentage of blood eosinophils tended to be higher than those 2 groups. MBP score of pECRS group was significantly higher than NECRS (p < 0.05), despite of smaller tissue eosinophil counts. Conclusion: pECRS might share some characteristics with ECRS although tissue eosinophil count was significantly smaller compared with ECRS. The results of this study have shown that MBP score in pECRS nasal polyps was significantly higher than NECRS patients and close to ECRS. That might suggest that eosinophils have existed in the nasal polyps of pPECRS patients at some point before surgery.

Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer.

BACKGROUND: Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. METHODS: We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I-III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. RESULTS: The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). CONCLUSIONS: These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.

1,2-Acyl migration with α-imino rhodium carbenoids leading to substituted 1-naphthols.

A unique method for the synthesis of substituted 1-naphthols by a rhodium(II)-catalysed ring-expansion reaction of 2-triazolyl-1-indanone derivatives is reported. 1,2-Acyl migration occurs with an intermediate α-imino rhodium carbenoid generated from the triazolyl moiety.

Photoassisted Cross-Coupling Reaction of α-Chlorocarbonyl Compounds with Arylboronic Acids.

A Suzuki-Miyaura cross-coupling reaction of α-chloroacetates or α-chloroacetamides with arylboronic acids is made possible by visible-light irradiation. This reaction provides a useful method for the synthesis of α-arylacetates and α-arylacetamides from chlorides under mild reaction conditions. An indole-3-acetic acid derivative that is the key intermediate of the plant hormone auxin can be synthesized from 1-Boc-indole in two steps by combining an iridium-catalyzed C-H borylation and a palladium-catalyzed cross-coupling reaction.

Obstructive and secretory complications of diverting ileostomy.

This review aimed to highlight the etiology, diagnosis, treatment, and prevention of obstructive and secretory complications associated with diverting ileostomy (DI). Obstructive complications at the stoma site are termed stoma outlet obstruction (SOO) or stoma-related obstruction (SRO). The incidence of SOO/SRO is 5.4%-27.3%, and the risk factors are multifactorial; however, the configuration of the stoma limb and the thickness of the rectus abdominis muscle (RAM) may be of particular concern. Trans-stomal tube decompression is initially attempted with a success rate of 33%-86%. A thick RAM may carry the risk of recurrence. Surgical refinement, including a wider incision of the anterior sheath and adequate stoma limb length, avoids tension and immobility and may decrease SOO/SRO. Secretory complications of DI are termed high output stoma (HOS). Persistent HOS lead to water and sodium depletion, and secondary hyperaldosteronism, resulting in electrolyte imbalances, such as hypomagnesemia. The incidence of HOS is 14%-24%, with an output of 1000-2000 mL/d lasting up to three days. Treatment of HOS is commenced after excluding postoperative complications or enteritis and includes fluid intake restriction, antimotility and antisecretory drug therapies, and magnesium supplementation. Intensive monitoring and surveillance programs have been successful in decreasing readmissions for dehydration.

Synthesis, Structure, and Dynamics of Chiral Eight-Membered Cyclic Molecules with Thienylene and Cyclopropylene Units Alternately Connected.

A rhodium(II)-catalyzed asymmetric cyclooligomerization of bifunctional monomers possessing triazolyl and vinyl groups at 2,3- and 3,4-positions on the thiophene ring is studied. Structurally interesting cyclic dimers in which thienylene and cyclopropylene units are alternately connected are obtained as the major components. The eight-membered rings in the center are non-planar and adopt a tub-shaped conformation. We also observe the phenomenon of racemization caused by a tub-to-tub ring-flipping, the activation energy of which is determined as 108 kJ mol-1 by electronic circular dichroism spectra measurement.

Stereo- and Enantioselective Synthesis of Propionate-Derived Trisubstituted Alkene Motifs.

We report a new method for constructing propionate-derived trisubstituted alkene motifs in a stereoselective manner. 1-Substituted 1,1-di(pinacolatoboryl)-(E)-alk-2-enes are generated in situ from 1-substituted 1,1-di(pinacolatoboryl)alk-3-enes through ruthenium(II)-catalyzed double-bond transposition. These species undergo a chiral phosphoric acid catalyzed allylation reaction of aldehydes to produce the E isomers of anti-homoallylic alcohols. On the other hand, the corresponding Z isomers of anti-homoallylic alcohols are obtained when a dimeric palladium(I) complex is employed as the catalyst for this double-bond transposition. Thus, both E and Z isomers can be synthesized from the same starting materials. A B-C(sp2 ) bond remaining with the allylation product undergoes the Suzuki-Miyaura cross-coupling reaction to furnish a propionate-derived trisubstituted alkene motif in a stereo-defined form. The present method to construct the motifs with (E)- and (Z)-alkenes are successfully applied to the syntheses of (+)-isotrichostatic acid, (-)-isotrichostatin RK, and (+)-trichostatic acid, respectively.

CD11c(+) dendritic cells coexpressing thymic stromal lymphopoietin receptor in animal model of eosinophilic otitis media.

BACKGROUND: Eosinophilic otitis media (EOM) is an intractable middle ear disease often associated with eosinophilic inflammatory airway conditions. Recently, dendritic cells (DCs) have been indicated as an essential component of Th2 allergic inflammation, such as bronchial asthma. DCs are activated by thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine. However, the relationship between TSLP and DCs in EOM remains unknown. OBJECTIVE: This study aimed to investigate the relationship between DCs and TSLP and to determine the involvement of DCs in EOM in an animal model. METHODS: Hartley guinea pigs were used as the animal model. Daily ovalbumin (OVA) stimulation of the middle ear was performed for 7 or 14 days. The temporal bone was dissected on the last day of stimulation, and paraffin-embedded sections were prepared. Immunostaining and immunofluorostaining for TSLP receptor (TSLPR) and CD11c, a surface marker of DCs, were performed. RESULTS: We found CD11c-immunopositive cells in the submucosal area of the middle ear epithelium, particularly around the eustachian tube. TSLPR-immunopositive cells exhibited a similar distribution as CD11c-positive cells. CONCLUSION: CD11c positive DCs coexpressing TSLPR were recruited after OVA challenge which might activate Th2 allergic reaction.

Chiral Macrocycles Having C3 Symmetry Resulting from Orientation of Thiophene Rings.

An chiral RhII -catalyzed cyclooligomerization reaction of thiophenes having triazolyl and vinyl substituents at the 2- and 4-positions was studied. Structurally interesting cyclic trimers, having chirality that is ascribed only to the orientation of the 2,4-disubstituted thiophene rings, are obtained. The 2,4-disubstitution of the starting thiophene monomer allows production of each of the enantiomers. The observed electronic circular-dichroism spectra are in accord with those simulated by density-functional theory calculations.

Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders.

Dermatologic disorders such as atopic dermatitis arise from genetic and environmental causes and are complex and multifactorial in nature. Among possible risk factors, aberrant immunological reactions are one of the leading etiologies. Immunosuppressive agents including topical steroids are common treatments for these disorders. Despite their reliability in clinical settings, topical steroids display side effects, typified by skin thinning. Accordingly, there is a need for alternate effective and well-tolerated therapies. As part of our efforts to investigate new immunomodulators, we have developed a series of JAK inhibitors, which incorporate novel three-dimensional spiro motifs and unexpectedly possess both excellent physicochemical properties and antidermatitis efficacy in the animal models. One of these compounds, JTE-052 (ent-60), also known as delgocitinib, has been shown to be effective and well-tolerated in human clinical trials and has recently been approved in Japan for the treatment of atopic dermatitis as the first drug among Janus kinase inhibitors.