Clinical Significance of Mesenteric Lymph Node Involvement in the Pattern of Liver Metastasis in Patients with Ovarian Cancer.

BACKGROUND: Mesenteric lymph node (MLN) involvement is often observed in ovarian cancer (OC) with rectosigmoid invasion. This study aimed to investigate the clinical significance of MLN involvement in the pattern of liver metastasis in patients with OC. METHODS: We included 85 stage II-IV OC patients who underwent primary or interval debulking surgery. Twenty-seven patients underwent rectosigmoid resection, whose status of MLN involvement was judged from hematoxylin and eosin (H&E) staining of resected specimens. The prognostic significance of clinicopathological characteristics, including MLN involvement, was evaluated using univariate and multivariate analyses. RESULTS: MLN involvement was detected in 14/85 patients with stage II-IV OC. Residual tumor status, cytology of ascites, and MLN involvement were independent prognostic factors for progression-free survival (PFS; p = 0.033, p = 0.014, and p = 0.008, respectively). When patients were classified into three groups (no MLN, one MLN, two or more MLNs), the number of MLNs involved corresponded to three distinct groups in PFS (p = 0.001). The 3-year cumulative incidence of liver metastasis of patients with MLN involvement was significantly higher than that of patients without MLN involvement (61.1% vs. 8.9%, p < 0.001). MLN involvement was significantly associated with liver metastasis of hematogenous origin (p < 0.001) compared with peritoneal disseminated origin. CONCLUSION: MLN involvement is an important prognostic factor in OC, predicting poor prognosis and liver metastasis of hematogenous origin.

[Laparoscopic Abdominoperineal Resection after Preoperative Chemoradiotherapy for Adenocarcinoma Associated with Anal Fistula].

A 72-year-old man had a chief complaint of anal pain and difficulty in defecation. He was diagnosed with adenocarcinoma by biopsy from a tumor of the anal canal. A computed tomography scan revealed neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa anal canal cancer. Preoperative capecitabine- based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. Digital rectal examination and imaging evaluation 8 weeks after preoperative CRT revealed that the tumor had shrunk. Fifteen weeks after preoperative CRT, laparoscopic abdominoperineal resection was performed. The pathological findings showed mucinous adenocarcinoma associated with anal fistula. At present, 12 months after the operation, no local recurrence and distant metastasis has been detected under follow-up evaluations.

Verification of the Japanese staging system for rectal cancer, focusing on differences with the TNM classification.

PURPOSE: The 9th Japanese Classification of Colorectal Cancer (9th JSCCR) has two main differences from the TNM classification (8th AJCC): first, main or lateral lymph node metastasis is classified as jN3; second, tumor nodules (ND) are treated as lymph node metastasis. In this study, we verified the 9th JSCCR for rectal cancer, focusing on the differences with the 8th AJCC. METHODS: This retrospective analysis involved 212 patients with stage I-III rectal cancer. ND was evaluated using whole-mount sections. We evaluated the relapse-free survival of each staging system, and compared the prognostic significance of the different staging systems using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). RESULTS: Main or lateral lymph node metastasis was detected in nine of 212 (4%) patients. ND was detected in 79 of 212 (37%) patients. The best risk stratification power was observed in the 9th JSCCR (AIC, 759; c-index, 0.708) compared with the 7th JSCCR (AIC, 771; c-index, 0.681), 8th JSCCR (AIC, 768; c-index, 0.696), and the 8th AJCC (AIC, 766; c-index, 0.691). CONCLUSIONS: The 9th JSCCR, which includes the concepts of jN3 and ND, is useful for the risk stratification of rectal cancer, and the contributes to precise decision-making for follow-up management and adjuvant therapy.

[A Case of 11-Year Patient Survival after the Resection of a Metastatic Pancreatic Tumor of Sigmoid Colon Cancer].

A 44-year-old woman underwent a sigmoidectomy for sigmoid colon cancer in March 2002. At 5 years after the primary surgery, she underwent 2 hepatectomies, 2 anastomotic resections, 1 lung resection, and 1 radiofrequency ablation. Computed tomography revealed a mass in the pancreatic tail in January 2008. We performed distal pancreatectomy. The specimen showed metastases ofthe sigmoid colon cancer. Computed tomography revealed metastases to the left iliac lymph node in September 2010. She underwent chemotherapy with IRIS for the lymph node metastases. After 16 chemotherapy sessions, the lymph node metastases disappeared. The patient is alive 11 years after the pancreatectomy. Resectable pancreatic metastasis from colorectal cancer is rare. Multimodal treatment that includes radical surgery may achieve long-term survival in some cases.

[A Case of a"Watch and Wait Therapy"Approach after Preoperative Chemoradiotherapy for Rectal Cancer Accompanied by Severe Emphysema].

A 72-year-old man was referred to our hospital for treatment for rectal cancer. Digital rectal examination and colonoscopy revealed a 4 cm tumor located at the anterior rectal wall 5 cm away from the anal verge, and pathological examination confirmed that the tumor was adenocarcinoma. A computed tomography scan detected neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa rectal cancer. The preoperative general examination revealed bradyarrhythmia and severe emphysema, and he was considered to be high risk for general anesthesia. After placement of a pacemaker, preoperative capecitabine-based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. The digital rectal examination and imaging evaluation 4 weeks after preoperative CRT revealed that the tumor disappeared, and pathological examination showed no malignant findings. Considering the risks of general anesthesia, the"watch and wait therapy"approach was adopted with sufficient informed consent. At present, 15 months after preoperative CRT, no evidence of regrowth or distant metastasis has been detected under rigorous follow- up evaluations.

[A Case of High-Frequency Microsatellite Instability in Colorectal Cancer with MSH2 Mutation Detected Using Gene Panel Testing with a Next-Generation Sequencer].

Here, we report about a woman in her 30s who had peritoneal dissemination and multiple colon cancer with high-frequency microsatellite instability(MSI-H). Her father, paternal grandfather, and maternal grandmother had a history of colorectal cancer treatment. Thus, Lynch syndrome was suspected. We performed R0 resection for peritoneal dissemination and subsequent peritoneal dissemination. A 435-gene panel testing using a next-generation sequencer identified MSH2 and other mutations in the tumor. Hence, we speculated that she could have a germline mutation of MSH2, which causes Lynch syndrome. In the future, if she wishes to receive genetic counseling and undergo germline testing for variants to confirm the diagnosis of Lynch syndrome, we will perform them after receiving informed consent.

[A Case of Long-Term Survival after Resection for Metachronous Liver and Lung Metastases of Rectal Cancer Associated with Familial Adenomatous Polyposis].

A 37-year-old man was admitted to our hospital for the treatment of familial adenomatous polyposis and rectal carcinoma. He underwent total colectomy with ileoanal anastomosis(pT3N1M0, pStage Ⅲa)followed by adjuvant therapy with S-1. Three months after primary surgery, CT and MRIrevealed liver metastases(S5, S6). Laparoscopic partial hepatectomy was performed. Two years after primary surgery, new liver metastases(S2, S8)were found and we performed open partial hepatectomy and administered mFOLFOX6. Three years and 5 months after primary surgery, right lung metastases(S6, S9) were detected and the patient underwent a thoracoscopic-assisted right lung wedge resection. Repeated resection of metastases might have contributed to the long-survival in our case.

[A Case of Long-Term Survival in a Patient with Advanced Rectal Cancer and Paraaortic and Lateral Lymph Node Metastases].

A 65-year-old woman was referred for further examination following positive results on a fecal occult blood test. Colonoscopy revealed type 0-Ⅱa cancer, with a lesion measuring 2 cm in diameter in the rectosigmoid colon, and type 5 cancer, with a lesion measuring 6 cm in diameter in the upper rectum. Computed tomography(CT)and positron emission tomography (PET)-CT revealed mesorectal lymph node metastases. Therefore, she was diagnosed with rectosigmoid colon cancer(Stage Ⅰ)and upper rectal cancer(Stage Ⅲa). However, PET-CT also revealed slight fluorodeoxyglucose uptake in the paraaortic and lateral lymph node lesions; hence, the possibility ofmetastasis could not be ruled out. Given that chemotherapy was restricted due to renal dysfunction, low anterior resection was performed as the first choice. Analysis of intraoperative frozen sections showed paraaortic and lateral lymph node metastases; thus, we performed lymph node dissection of these lesions. Pathological examination ofthe resected lymph nodes revealed that 21 of 37 lesions were cancer metastases. S-1 was administered as adjuvant chemotherapy for 5 months. Mediastinal lymph node metastases was suspected on chest CT 5 months and 3 years post-surgery; thus, panitumumab was administrated. These lymph nodes decreased in size immediately. Six years after the first surgery, the patient was well without any signs of recurrence.

[A Case of Pathological Complete Response with Neoadjuvant Chemotherapy for Advanced Rectal Cancer].

A 62-year-old man was admitted with complaints of bloody stool. Colonoscopy revealed a 5 cm diameter type 2 tumor in the lower rectum close to the anal canal. Tumor biopsy indicated a well-differentiated tubular adenocarcinoma. Computed tomography revealed locally advanced rectal cancer with mesorectal lymph node metastases(cT3N1P0M0, Stage Ⅲa, JSCCR 8th). The patient was treated with neoadjuvant chemotherapy(NAC)after transverse colostomy as an anus-preserving procedure. For the NAC, 12 courses of capecitabine plus oxaliplatin(CapeOX)and bevacizumab(BV)were administered. Colonoscopy after NAC revealed that the main tumor had considerably shrunk. No malignant tissues were found on biopsy. However, rectal wall thickness remained unchanged. Therefore, response evaluation for chemotherapy indicated partial response. Intersphincteric resection(ISR)with diverting loop ileostomy was performed as an anus-preserving surgical procedure. No remnant tumor in the rectum or lymph node metastases were found upon the pathological examination of resected specimens. Ileostomy closure was performed at 6 months post-ISR. At 12 months post-ISR, the patient was well and showed no signs of recurrence. This case demonstrated that NAC with CapeOX and BV can be a promising option for treating locally advanced lower rectal cancer and preserving the anus.

[Staged Laparoscopy-Assisted Surgery Including Hand-Assisted Laparoscopic Surgery for Rectal Cancer with Synchronous Liver Metastases-A Case Report].

Here, we reported a case of a 39-year-old woman having rectal cancer with multiple liver metastases who underwent staged laparoscopic resection. She was diagnosed with low rectal cancer and multiple liver metastases; thus, she underwent low anterior resection and diverting colostomy. Following the neoadjuvant chemotherapy, she underwent colostomy closure and subsequent hand-assisted laparoscopic partial hepatectomy using the operative site during the colostomy closure. The postoperative course was uneventful, and adjuvant chemotherapy with CapeOX was performed 3 weeks post-surgery. Minimally invasive surgery was performed using hand-assisted laparoscopy.

[A Case of Long-Term Survival in a Patient with Ascending Colon Cancer and Synchronous Multiple Liver Metastases after Multimodality Therapy Including Multiple Hepatectomy].

We present a case of long-term survival in a patient with advanced ascending colon cancer and multiple liver metastases after receiving multimodality therapy, which included hepatic atrial infusion(HAI)and 4 hepatectomies. At diagnosis, the 65- year-old woman underwent right hemicolectomy for advanced ascending colon cancer with multiple liver metastases (T3N1M1[H2], Stage Ⅳ). The 11 liver metastatic lesions were treated by weekly HAI of 5-fluorouracil(5-FU). The lesions reduced in size(response rate 28.9%)immediately following treatment, and no new lesions were detected, but 10 months after treatment the size of the S2 tumor had increased. Systemic chemotherapy with irinotecan and S-1 was administered. Continued development of the S2 tumor in the liver prompted a radical lateral segment hepatectomy. Four months later, a computed tomography(CT)scan revealed a S6 tumor of the liver, for which a posterior segment hepatectomy was performed. A CT scan showing a S1 tumor in the liver 9 months later resulted in chemotherapeutic treatment with CapeOX, followed by mFOLFOX6. Despite treatment, the S1 tumor developed further, prompting a S1 partial hepatectomy. A further partial S8 hepatectomy was performed 7 years after surgery for the primary lesion following a CT scan that revealed a S8 tumor in the liver. There has been no recurrence of tumors in the 5 years and 5 months since this last hepatectomy.

[A Case of Resistance to Systemic Therapy in Hypermutation of Colorectal Cancer].

A 78-year-old man was admitted with diarrhea. Colonoscopy and computed tomography(CT)revealed rectal cancer with multiple liver metastases. Low anterior resection was performed for local control. After the operation, 5 courses of mFOLFOX6 plus bevacizumab chemotherapy were administered as first-line systemic therapy, but CT showed progressive disease with liver metastases. After the first-line systemic therapy, 2 courses of FOLFIRI plus bevacizumab chemotherapy were performed as second-line systemic therapy, but CT also revealed progressive disease with liver metastases. We retrospectively performed comprehensive genomic sequencing with a 415-gene panel and found that the patient had a hypermutation subtype. Interestingly, the panel also revealed that he had mismatch-repair(MMR)deficiency with MSH2 mutation, which is reported as a possible cause of resistance to 5-fluorouracil in colorectal cancer.

[A Case of Long-Term Survival after Repeated Peritoneal Recurrences of Perforated Sigmoid Colon Cancer Treated with Systemic Chemotherapy and R0 Resection of Peritoneal Tumors].

We report here a case of long-term survival with repeated peritoneal recurrences after resection of perforated sigmoid colon cancer. A 65-year-old man presented with diarrhea and abdominal pain. Computed tomography(CT)revealed diffuse peritonitis caused by perforated sigmoid colon cancer. We performed sigmoidectomy with D2 lymphadenectomy and descending colostomy. Postoperatively, S-1 was administered for 12 months as adjuvant chemotherapy. CT showed peritoneal nodules 56 months after the surgery. After 10 courses of mFOLFOX6 plus bevacizumab, the tumors decreased in size (reduction rate of 34.4%; a partial response). Subsequently, 3 peritoneal nodules were resected with curative intent. Another peritoneal nodule was detected 57 months after the second surgery. After 3 courses of XELOX plus bevacizumab, the nodule decreased in size(reduction rate of 69.0%; a partial response). The nodule was resected with a curative intent. At the last follow-up 135 months after the first surgery, the patient remains alive with no evidence of disease.

Lithium binaphtholate-catalyzed asymmetric addition of lithium acetylides to carbonyl compounds.

The asymmetric addition of lithium acetylides to carbonyl compounds in the presence of a chiral lithium binaphtholate catalyst was developed. A procedure involving the slow addition of carbonyl compounds to lithium acetylides improved the enantioselectivity. This reaction afforded diverse chiral secondary and tertiary propargylic alcohols in high yields and with good to high enantioselectivities.

Sugar-regulated cation channel formed by an insect gustatory receptor.

Insects sense the taste of foods and toxic compounds in their environment through the gustatory system. Genetic studies using fruit flies have suggested that putative seven-transmembrane gustatory receptors (Grs) expressed in gustatory sensory neurons are required for responses to specific tastants. We reconstituted sugar responses of Bombyx mori Gr-9 (BmGr-9), a silkworm Gr, in two heterologous expression systems. Xenopus oocytes or HEK293T cells expressing BmGr-9 selectively responded to D-fructose with an influx of extracellular Ca(2+) and a nonselective cation current conductance in a G protein-independent manner. Outside-out patch-clamp recording of BmGr-9-expressing cell membranes provides evidence supporting the hypothesis that BmGr-9 constitutes a ligand-gated ion channel. The fructose-activated current associated with BmGr-9 was suppressed by other hexoses, including glucose and sorbose. The activation and inhibition of insect Gr ion channels may be the molecular basis for the decoding system that discriminates subtle differences in sweet taste. Finally, Drosophila melanogaster Gr43a (DmGr43a), a BmGr-9 ortholog, also responded to D-fructose, suggesting that DmGr43a relatives appear to compose the family of fructose receptors.

Improving Visualization of In-stent Lumen Using Prototype Photon-counting Detector Computed Tomography with High-resolution Plaque Kernel.

The study aimed to compare the performance of photon-counting detector computed tomography (PCD CT) with high-resolution (HR)-plaque kernel with that of the energy-integrating detector CT (EID CT) in terms of the visualization of the lumen size and the in-stent stenotic portion at different coronary vessel angles. The lumen sizes in PCD CT and EID CT images were 2.13 and 1.80 mm at 0°, 2.20 and 1.77 mm at 45°, and 2.27 mm and 1.67 mm at 90°, respectively. The lumen sizes in PCD CT with HR-plaque kernel were wider than those in EID CT. The mean degree of the in-stent stenotic portion at 50% was 69.7% for PCD CT and 90.4% for EID CT. PCD CT images with HR-plaque kernel enable improved visualization of lumen size and accurate measurements of the in-stent stenotic portion compared to conventional EID CT images regardless of the stent direction.

Iterative reconstruction with multifrequency signal recognition technology to improve low-contrast detectability: A phantom study.

Background: Brain CT needs more attention to improve the extremely low image contrast and image texture. Purpose: To evaluate the performance of iterative progressive reconstruction with visual modeling (IPV) for the improvement of low-contrast detectability (IPV-LCD) compared with filtered backprojection (FBP) and conventional IPV. Materials and methods: Low-contrast and water phantoms were used. Helical scans were conducted with the use of a CT scanner with 64 detectors. The tube voltage was set at 120 kVp; the tube current was adjusted from 60 to 300 mA with a slice thickness of 0.625 mm and from 20 to 150 mA with a slice thickness of 5.0 mm. Images were reconstructed with the FBP, conventional IPV, and IPV-LCD algorithms. The channelized Hotelling observer (CHO) model was applied in conjunction with the use of low-contrast modules in the low-contrast phantom. The noise power spectrum (NPS) and normalized NPS were calculated. Results: At the same standard and strong levels, the IPV-LCD method improved low-contrast detectability compared with the conventional IPV, regardless of contrast-rod diameters. The mean CHO values at a slice thickness of 0.625 mm were 1.83, 3.28, 4.40, 4.53, and 5.27 for FBP, IPV STD, IPV-LCD STD, IPV STR, and IPV-LCD STR, respectively. The normalized NPS for the IPV-LCD STD and STR images were slightly shifted to the higher frequency compared with that for the FBP image. Conclusion: IPV-LCD images further improve the low-contrast detectability compared with FBP and conventional IPV images while maintaining similar FBP image appearances.

Gene panel testing detects important genetic alterations in ulcerative colitis-associated colorectal neoplasia.

Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

Diverse meibum lipids produced by Awat1 and Awat2 are important for stabilizing tear film and protecting the ocular surface.

A lipid layer consisting of meibum lipids exists in the tear film and functions in preventing dry eye disease. Although the meibum lipids include diverse lipid classes, the synthesis pathway and role of each class remain largely unknown. Here, we created single and double knockout (KO and DKO, respectively) mice for the two acyl-CoA wax alcohol acyltransferases (Awat1 and Awat2) and investigated their dry eye phenotypes and meibum lipid composition. Awat2 KO and DKO mice exhibited severe dry eye with meibomian gland dysfunction, whereas Awat1 KO mice had mild dry eye. In these mice, specific meibum lipid classes were reduced: (O-acyl)-ω-hydroxy fatty acids and type 1ω wax diesters in Awat1 KO mice, wax monoesters and types 1ω and 2ω wax diesters in Awat2 KO mice, and most of these in DKO mice. Our findings reveal that Awat1 and Awat2 show characteristic substrate specificity and together produce diverse meibum lipids.