Clinical significance of the post/preoperative anti-p53 antibody ratio in predicting the prognosis of patients with colorectal cancer after curative surgery and its usefulness in combination with carcinoembryonic antigen.

[Introduction] Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. [Methods] In total, 1,223 patients with stage I-III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within one month preoperatively and three months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. [Results] Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival (RFS) than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. [Conclusion] In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups.

Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein.

Quinoxaline is one of the privileged heterocyclic fragments for drug molecules. Quinoxaline anticancer drug candidates XK469 and CQS exhibit antiproliferative and proapoptotic properties against various cancers. Based on their chemical structures, we therefore synthesized a series of quinoxaline-1,3,4-oxadiazole hybrids and assessed their anticancer potential on human leukemia HL-60 cells. Although these hybrids exerted significant inhibition of HL-60 cell proliferation, they showed high cytotoxicity on human normal cells (WI-38). Utilizing information from molecular modelling of the hybrids to the anti-apoptotic Bcl-2 protein, we added substructures including phenyl, piperazine, piperidine, and morpholine rings to their frameworks. The designed quinoxaline-1,3,4-oxadiazole hybrid derivatives successfully induced apoptotic response on HL-60 cells with low toxicity on WI-38 cells. Furthermore, RT-PCR analysis demonstrated that these derivatives predominantly inhibit Bcl-2 expression. Our findings highlight the great potential for the development of synthetic quinoxaline-1,3,4-oxadiazole hybrid derivatives as proapoptotic anticancer agents.

Synthesis of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as potent antiproliferative agents via a hybrid pharmacophore approach.

Imiquimod (1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine) is efficacious in topical therapy for certain types of skin cancers. Structurally similar EAPB0203 (N-methyl-1-(2-phenethyl)imidazo[1,2-a]quinoxalin-4-amine) has been shown higher in vitro potency than imiquimod. Besides, triazole, oxadiazole, and thiadiazole rings are privileged building blocks in drug design. A series of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole and [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-thiadiazole derivatives were therefore synthesized by incorporation of these rings into the structure of EAPB0203 and assessed their antiproliferative effects against various cancer cell lines. The 1,3,4-oxadiazole derivatives demonstrated the superior effectiveness compared to imiquimod and EAPB0203. Our findings highlight the excellent potential of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as anticancer agents.

[Case of Spindle Cell Carcinoma of the Breast Resistant Neoadjuvant Chemotherapy].

We report a rare case of spindle cell carcinoma of the breast which grew rapidly during neoadjuvant chemotherapy. A 72- year-old female was presenting with chief complaint of a mass in the right breast; a tumor about 20 mm in size. Core needle biopsy of tumor revealed invasive ductal carcinoma and fine needle aspiration cytology of axillary lymph node was Class Ⅴ. So she was diagnosis breast cancer as cT2N1M0, cStage ⅡB. The tumor subtype was triple negative breast cancer (TNBC). She received the neoadjuvant chemotherapy by FEC100. After FEC 4 courses, we detected a huge and rapid growing breast mass of 40 mm by CT. She was administered received mastectomy and axillary lymph node dissection after 4 months from initial contact. Pathological finding was spindle cell carcinoma of the breast. Postoperatively, she was treated with weekly PTX for a total of 12 courses and radiation therapy for a right chest wall and supraclavicular fossa. Although the tumor was resistant for neoadjuvant chemotherapy, she is alive and well without metastasis for more than 3 years.

[Resected Metachronous Pancreatic Metastasis from Rectal Cancer-A Case Report].

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

[A Case of Early-Developing Rapidly Progressive Glomerulonephritis after Laparoscopic-Assisted Distal Gastrectomy for Gastric Cancer].

This is a case of a 76-year-old man who had no significant past medical or family history. In the current medical history, in November 2017, upper gastrointestinal endoscopy showed a semicircular protruding lesion in the posterior wall of the gastric antrum, and gastric cancer was diagnosed following biopsy. Endoscopic submucosal dissection(ESD)was performed in the same year for the treatment of gastric cancer(cT1aN0M0). Pathological findings after ESD treatment showed invasion into the submucosa requiring non-curative resection. For this reason, laparoscopic pylorus side gastrectomy(D1 dissection)and Billroth Ⅰ reconstruction were performed as additional procedures in March 2018. The patient was discharged on the 10th postoperative day and was followed-up on an outpatient basis. On the postoperative day 14, he was re-admitted with complaints of upper abdominal pain and exacerbation of inflammation. Medical treatment, such as antibiotic administration was followed, however, a high degree of inflammatory response, renal dysfunction, and occult blood in urine were observed. Because of suspicion of vasculitis-related nephritis, the case was diagnosed as anti-GBM antibody type rapid progressive nephritis. We came across a case of rapidly progressive glomerulonephritis after laparoscopic pylorus side gastrectomy performed for early gastric cancer, and hence, We will review the related literature.

[A Case Report of Retroperitoneal Liposarcoma Resected Six Times for 16 Years].

We report of a long-surviving patient with retroperitoneal liposarcoma that required 6 surgeries in 16 years. A 62-year-old man was diagnosed with liposarcoma, which was first excised in 2001. Thereafter, we excised recurrences in the retroperitoneum with the left kidney in February 2004. We excised recurrences with the left half of the colon in November 2007 and February 2010 and recurrences with a part of the intestine in November 2014. This time, we excised recurrences under the right abdominal rectus muscle and near the left half of the colon. The pathological diagnosis was well-differentiated liposarcoma. There is currently no evidence of recurrence 16 years after the first recurrence excision. In this case, active excision of recurrences and identification of high-grade dedifferentiated-type liposarcomas were factors of long survival.

[A Case Report of Laparoscopy-Assisted Distal Gastrectomy for Early Gastric Cancer with Abortive Behçet Disease].

A 32-year-old woman with a history of undergoing upper gastrointestinal surgery was administered prednisolone for abortive Behçet's disease since 2015. In March 2017, upper gastrointestinal endoscopy revealed a 0-IIc type early stage gastric carcinoma at the posterior wall of the gastric antrum. The pathological diagnosis was signet-ring cell carcinoma. This gastric carcinoma was classified as cT1aN0M0; therefore, endoscopic submucosal dissection(ESD)was performed for the expanded indication lesion in April 2017. The pathological diagnosis after ESD indicated the need for non-curative resection; thus, laparoscopy-assisted distal gastrectomy and Billroth I anastomosis were performed in July 2017. A transient anastomotic structure was admitted after this surgery, but she was discharged from the hospital lighthearted. A preoperative important aspect was the careful examination of all intestinal tracts for ulcer lesions, and an intraoperative important aspect was hand-sewn anastomosis because using a metallic stapler conferred a high risk of ulcer lesions and suture failure. We encountered a case wherein laparoscopy-assisted distal gastrectomy was performed in a patient with abortive Behçet's disease, early stage gastric carcinoma, and a history of undergoing upper gastrointestinal surgery.

[A Case of Advanced Gastric Cancer with Long-Term Survival Due to Successful Ramucirumab and Paclitaxel Therapy].

This is a case of a 70-year-old man. Two courses of docetaxel/cisplatin/S-1 combination therapy were administered after clinical trial registration with diagnosis of Stage Ⅳ gastric cancer(ypT3N3aM1). In June 2014, gastrectomy and splenectomy were performed. Postoperative S-1 adjuvant chemotherapy was administered; however, in September 2014, aorticl ymph node metastasis was diagnosed as recurrent. After recurrence, irinotecan/cisplatin therapy was administered. In February 2015, recurrent lymph node metastasis increased, and chemotherapy was changed to paclitaxel. In May 2015, numbness (Grade 2)of the fingers was observed, and treatment was changed to oxaliplatin/S-1. In February 2016, storage of ascites became remarkable; therefore, chemotherapy was discontinued as per policy. After that, we continued outpatient visit and observed increased recurrent lymph node metastasis on image evaluation; however, as the patient's general condition was good, chemotherapy was restarted. Ramucirumab/paclitaxel therapy started in February 2017. During the course of treatment, neutropenia(Grade 2)was observed as an adverse event, but therapy continuation was possible without loss of ramucirumab only with loss of paclitaxel. Thereafter, the recurrence of lymph node metastasis was reduced, and the ascites accumulation decreased. Until now, 1 year after the start of ramucirumab/paclitaxel therapy, the patient still visits the outpa- tient clinic.

Primary omental smooth muscle tumor in an adult male: a diagnostic dilemma for leiomyoma: a case report.

BACKGROUND: The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient. CASE PRESENTATION: A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up. DISCUSSION AND CONCLUSION: We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research.

Heme degradation by Staphylococcus aureus IsdG and IsdI liberates formaldehyde rather than carbon monoxide.

IsdG and IsdI from Staphylococcus aureus are novel heme-degrading enzymes containing unusually nonplanar (ruffled) heme. While canonical heme-degrading enzymes, heme oxygenases, catalyze heme degradation coupled with the release of CO, in this study we demonstrate that the primary C1 product of the S. aureus enzymes is formaldehyde. This finding clearly reveals that both IsdG and IsdI degrade heme by an unusual mechanism distinct from the well-characterized heme oxygenase mechanism as recently proposed for MhuD from Mycobacterium tuberculosis. We conclude that heme ruffling is critical for the drastic mechanistic change for these novel bacterial enzymes.

A Case of Colon Cancer with Extramural Tumor Deposits in the Main Lymph Node Area: A Case Report.

A 72-year-old man with type 2 sub-circumferential tumors in the descending colon and two nodules around the pedicle of the inferior mesenteric artery (main lymph node area) underwent laparoscopic left hemicolectomy with D3 lymphadenectomy. Two lymph nodes around the inferior mesenteric artery pedicle were completely excised. Pathological examination revealed a moderately differentiated tubular adenocarcinoma. Nodules were only found in the main lymph node area, and no lymph node structures were observed in these nodules. These tumor deposits (TDs) may be extramural TDs without lymph node structure or lymph node skip metastasis. The presence of TDs in colorectal cancer is associated with an adverse prognosis, and the requirement of chemotherapy in such cases should be examined. Therefore, it is important to correctly recognize TDs and categorize the disease into a high- or low-risk group within stage III. We report this case because it is necessary to review the definition of TDs, and the assessment of extramural TDs remains controversial.

Laser-polarization effects on coherent vibronic excitation of molecules with quasi-degenerate electronic states.

The laser-polarization effects on nonadiabatically coupled π-electron rotation (ring current) and molecular vibration have been theoretically analyzed for aromatic molecules with quasi-degenerate excited states irradiated by an ultrashort laser pulse of arbitrary polarization. We first derived general formulations of the coherent electronic wave packet and expectation value of electronic angular momentum within a frozen-nuclei model. The relative quantum phase of the superposed quasi-degenerate states, which determines the oscillating behavior of angular momentum, can be manipulated by the ellipticity and orientation of the incident laser. Nuclear wave packet simulations with a model molecule confirmed the controllability of π-electron rotation, although the angular momentum is gradually reduced by nonadiabatic couplings. The amplitude of molecular vibration depends prominently on the orientation of linear polarization vectors rather than the helicity of circular polarization. The characteristic feature in vibrational amplitudes is attributed to the interference in nonadiabatic transition governed by the relative quantum phase between nuclear wave packets. This offers a new strategy for laser control of molecular vibrations through the wave packet interference in nonadiabatic transition.

Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II/III colorectal cancer.

Purpose: This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. Methods: We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II/III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. Results: The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and T pathological (pT) factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). Conclusion: Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

Functionalization of coordination nanochannels for controlling tacticity in radical vinyl polymerization.

Systematic functionalization of porous coordination polymers (PCPs), [Cu(2)(L)(2)(ted)](n) (where L = dicarboxylates and ted = triethylenediamine), by introducing various substituents onto the component organic ligand, L, was performed to regulate the radical polymerization of methyl methacrylate (MMA) in the nanochannels. The effect of the substituent groups on stereoregularity of the resulting poly(methyl methacrylate) (PMMA) was observed, where the tacticity of the PMMA strongly depended on the number and position of the substituent. In particular, polymerization of MMA in [Cu(2)(2,5-dimethoxyterephthalate)(2)(ted)](n) gave PMMA with high isotactic and heterotactic triad fractions, which is one of the most effective systems for changing the tacticity of PMMA in radical polymerization. To understand the mechanism of this drastic stereoregularity change, a variety of experimental and theoretical analyses, such as IR, N(2) adsorption, a statics study, and molecular dynamics (MD) calculations, were performed. Accurate MD calculations were helpful to determine the most plausible structures of [Cu(2)(L)(2)(ted)](n) and revealed that the specific channel shape of [Cu(2)(2,5-dimethoxyterephthalate)(2)(ted)](n) induces the large tacticity change of the resulting PMMA.

Modified Glasgow Prognostic Score and Carcinoembryonic Antigen Predict Poor Prognosis in Elderly Patients with Colorectal Cancer.

OBJECTIVE: To investigate the prognostic values of the preoperative modified Glasgow Prognostic Score (mGPS) and carcinoembryonic antigen (CEA) alone and combined in elderly patients with colorectal cancer (CRC) planning to receive curative surgery. METHODS: We retrospectively analyzed 130 elderly patients (aged ≥80 years) with CRC who received curative surgery between 2008 and 2016. The preoperative mGPS and CEA levels were calculated. RESULTS: Elevated preoperative mGPS or CEA level was significantly associated with shorter relapse-free survival (p = 0.005, both) and cancer-specific survival (p = 0.011 and p < 0.001, respectively). Combined use of these two factors improved the predictive accuracy for tumor recurrence relative to that of either factor. CONCLUSION: Both mGPS and CEA were independent prognostic factors of CRC in elderly patients receiving curative surgery, but their combination was more accurate.

[Epiphora in a patient receiving FOLFOX therapy].

A 75-year-old patient with colorectal cancer was treated by FOLFOX4 therapy. When the total dose of 5-fluorouracil reached 21,200 mg and the total dose of oxaliplatin reached 880 mg after about 100 days of treatment, epiphora developed. Because the pharmacist discovered it soon, he could consult with an ophthalmologist, and the man was diagnosed with subconjunctival hemorrhage. Thereafter, the symptom improved with ofloxacin eye drops. Attention must be paid to the visual side effect in case an anticancer agent is used and when aggressive involvement of the pharmacist in medical team treatment is expected.