Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

Objective: The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinumbased chemotherapy in ovarian cancer. Methods: We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results: NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters. Conclusion Serum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.

Objective: The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinumbased chemotherapy in ovarian cancer. Methods: We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results: NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters. Conclusion Serum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.

Although palliative sedation therapy (PST) is considered to alleviate intolerable and refractory symptoms in dying patients with advanced cancer, there have been few studies regarding the situation of tertiary cancer center. We conducted a retrospective survey of the medical records of the patients who died between April 2015 and March 2016 at the National Cancer Center Hospital in Japan. PST was conducted in 75 out of 431 patients (17.4%). The patient demographics were as follows: sex (male/female), 48/27; median age, 61 years (range 5-83; 11 patients (14.7%) were aged under 39 years); and primary sites were lung, 18 (24.7%)/ pancreas, 11 (14.7%)/ hematopoietic organs, 11 (14.7%)/ bones and soft tissues, 8 (10.7%)/ and the others, 27 (36.0%). The main target symptoms for PST were dyspnea (38, 50.7%) and delirium (30, 40.0%). The most commonly used sedative agent was midazolam (72, 96.0%). Continuous deep sedation was intended in 61 patients (81.3%) at the death. Median survival from the start of PST were 2 days (range 0-54). The differences between palliative care team (PCT) intervention group and control group were lower age (58 vs. 62.5, P=0.048) and uniformity of initial midazolam dose (5-12 vs. 9.6-25.2 mg/day). Distinctive feature in this study was large proportion of adolescent and young adult patients with rare cancers. PCT might have different approaches to sedation in comparison to non-PCT medical staffs.

We previously described a rare case of anaphylaxis presumably induced by carminic acid in cochineal dye used as a food additive. In this study, highly pure carminic acid was added to an albumin-containing buffer at various concentrations, followed by serial dilution. Varying the mixing ratio of carminic acid and albumin affected the extent of histamine release from passively sensitized basophils. Similar basophil histamine release occurred with carminic acid-globulin solutions. These results provide experimental evidence indicating that basophil activation is dependent on hapten (carminic acid) and carrier (protein) interaction.
Anaphylaxis ; Basophils ; Carmine ; Food Additives ; Histamine Release ; Hypersensitivity ; In Vitro Techniques

OBJECTIVE: Carcinosarcoma of the uterine corpus has a poor prognosis. Although pathological necrosis is a prognostic factor of endometrial cancer, the clinicopathological influences of an unenhanced region observed on magnetic resonance imaging (MRI) are inconclusive. The aim of our study was to determine the clinicobiological impact of the presence of an unenhanced region on MRI, which can represent necrosis, in uterine carcinosarcoma. METHODS: The clinicopathological factors of 29 patients diagnosed with uterine carcinosarcoma were assessed retrospectively. The percentage of the tumor that was unenhanced on MRI was determined. The clinicopathological factors related to the unenhanced regions were evaluated. The prognostic significance was assessed using the Kaplan-Meier method and Cox regression model. RESULTS: Although the presence of pathological necrosis was not a poor prognostic factor (p=0.704), unenhanced regions on MRI correlated with poor prognosis when the unenhanced regions in the tumor accounted for more than 10% of the total tumor (p=0.019). The percentage of unenhanced regions was positively correlated with stage (p=0.028; r=0.4691) and related to tumor size (p=0.086; r=0.3749). The Cox regression analysis indicated that the presence of lymph node (LN) metastasis and more than 10% of the tumor being unenhanced on MRI were prognostic factors of overall survival in the univariate analyses (p=0.018 and p=0.047, respectively). CONCLUSION: The unenhanced region on MRI, which represents pathological necrosis, reflects tumor progression, and semi-quantification of the region is useful to predict the prognosis in patients with uterine carcinosarcoma.
Carcinosarcoma* ; Endometrial Neoplasms ; Female ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging* ; Methods ; Necrosis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Uterine Neoplasms

OBJECTIVE: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. METHODS: Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis. RESULTS: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028). CONCLUSION: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer.
Adult ; Aged ; Aged, 80 and over ; Female ; *Groin ; Humans ; Lymph Node Excision ; Lymphatic Metastasis/pathology ; Magnetic Resonance Imaging ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node/*pathology ; Sentinel Lymph Node Biopsy/*methods ; Vulvar Neoplasms/*pathology/surgery

BACKGROUND: Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment. METHODS: A total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3+/-35.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively. RESULTS: After 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167+/-63 to 151+/-49 mg/dL (P<0.01), and from 7.5%+/-1.3% to 6.9%+/-0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease. CONCLUSION: Most suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.
Blood Glucose ; Body Mass Index ; Coronary Artery Disease ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Dipeptidyl-Peptidase IV Inhibitors ; Hemoglobin A, Glycosylated ; Humans ; Retrospective Studies ; Treatment Outcome

Objective:Delayed gastric emptying (DGE) after pylorus-preserving pancreatoduodenectomy (PpPD) is a persistent and frustrating complication. To preserve pylorus ring with denervation and devascularization may be a risk factor of DGE after pancreaticoduodenectomy. We conducted this study to confirm the hypothesis that pylorus-resecting pancreatoduodenectomy (PrPD) reduces the incidence of DGE compared to PpPD. Moreover, long-term outcomes of PrPD and the adverse effect of postsurgical DGE on long-term outcomes have not been reported. Therefore, in addition, this study focused on long-term outcomes during 24 months after surgery between PrPD versus PpPD. Methods: Between October 2005 and March 2009, at Wakayama Medical University Hospital (WMUH), 130 patients with pancreatic or periampullary lesions were randomized to preservation of the pylorus ring (PpPD) or to resection of the pylorus ring (PrPD). In PpPD, the proximal duodenum was divided 3-4cm distal to the pylorus ring. In PrPD, the stomach was divided just adjacent the pylorus ring and the nearly total stomach more than 95% was preserved. Shortterm and long-term outcomes were evaluated between PpPD and PrPD. Primary endpoint is the incidence of DGE. DGE was defined according to a consensus definition and clinical grading about postoperative DGE proposed by the international study group of pancreatic surgery (ISGPS). This RCT was registered at Clinical Trials.Gov NCT00639314. Results: Of 130 patients who were enrolled in this study, 64 patients were randomized to PpPD and 66 to PrPD. The overall incidence of DGE in this RCT was 10.8% (14 of 130 patients); the overall incidence of DGE was significantly lower in PrPD (4.5%) than PpPD (17.2%) (P =0 .0244). DGE was classified into three categories proposed by the International Study Group of Pancreatic Surgery. The proposed clinical grading classified 11 cases of DGE in PpPD into grades A (n=6), B (n=5), and C (n=0), and one case in PrPD into each of the three grades. In long-term outcomes, weight loss > grade 2 (Common Terminology Criteria for Adverse Events, Ver. 4.0) at 24 months after surgery improved significantly in PrPD (16.2%) compared with PpPD (42.2%) (P = 0.011). Nutritional status and late postoperative complications were similar between PpPD and PrPD. The incidence of weight loss greater than Grade 2 at 24 months after surgery was 63.6% in patients with DGE group and 25.3% in patients without DGE group (P = 0.010). Tmax (the time to peak 13CO2 content in 13C-acetate breath test) at 24 months after surgery in patients with DGE was significantly delayed compared with those without DGE (27.9 ± 22.7min vs.16.5 ± 10.1min, P=0.023). Serum albumin at 24 months after surgery was higher in patients without DGE than those with DGE (3.7±0.6 g/dl vs. 4.1±0.4 g/dl, P=0.013). Conclusion: This study clarified that PrPD can lead to a significant reduction in the incidence of DGE compared with PpPD. Moreover, PrPD offers similar longterm outcomes with PpPD. DGE may be associated with weight loss and poor nutritional status in long-term outcomes.

Objective:Delayed gastric emptying (DGE) after pylorus-preservingpancreatoduodenectomy (PpPD) is a persistent and frustrating complication. Topreserve pylorus ring with denervation and devascularization may be a risk factorof DGE after pancreaticoduodenectomy. We conducted this study to confirm thehypothesis that pylorus-resecting pancreatoduodenectomy (PrPD) reduces theincidence of DGE compared to PpPD. Moreover, long-term outcomes of PrPDand the adverse effect of postsurgical DGE on long-term outcomes have not beenreported. Therefore, in addition, this study focused on long-term outcomes during24 months after surgery between PrPD versus PpPD.Methods: Between October 2005 and March 2009, at Wakayama MedicalUniversity Hospital (WMUH), 130 patients with pancreatic or periampullarylesions were randomized to preservation of the pylorus ring (PpPD) or to resectionof the pylorus ring (PrPD). In PpPD, the proximal duodenum was divided 3-4cmdistal to the pylorus ring. In PrPD, the stomach was divided just adjacent thepylorus ring and the nearly total stomach more than 95% was preserved. Shorttermand long-term outcomes were evaluated between PpPD and PrPD. Primaryendpoint is the incidence of DGE. DGE was defined according to a consensusdefinition and clinical grading about postoperative DGE proposed by theinternational study group of pancreatic surgery (ISGPS). This RCT was registeredat Clinical Trials.Gov NCT00639314.Results: Of 130 patients who were enrolled in this study, 64 patients wererandomized to PpPD and 66 to PrPD. The overall incidence of DGE in this RCTwas 10.8% (14 of 130 patients); the overall incidence of DGE was significantlylower in PrPD (4.5%) than PpPD (17.2%) (P =0 .0244). DGE was classified intothree categories proposed by the International Study Group of Pancreatic Surgery.The proposed clinical grading classified 11 cases of DGE in PpPD into grades A(n=6), B (n=5), and C (n=0), and one case in PrPD into each of the three grades.In long-term outcomes, weight loss > grade 2 (Common Terminology Criteriafor Adverse Events, Ver. 4.0) at 24 months after surgery improved significantlyin PrPD (16.2%) compared with PpPD (42.2%) (P = 0.011). Nutritional statusand late postoperative complications were similar between PpPD and PrPD. Theincidence of weight loss greater than Grade 2 at 24 months after surgery was63.6% in patients with DGE group and 25.3% in patients without DGE group (P= 0.010). Tmax (the time to peak 13CO2 content in 13C-acetate breath test) at24 months after surgery in patients with DGE was significantly delayed comparedwith those without DGE (27.9 ± 22.7min vs.16.5 ± 10.1min, P=0.023). Serumalbumin at 24 months after surgery was higher in patients without DGE than thosewith DGE (3.7±0.6 g/dl vs. 4.1±0.4 g/dl, P=0.013).Conclusion: This study clarified that PrPD can lead to a significant reduction inthe incidence of DGE compared with PpPD. Moreover, PrPD offers similar longtermoutcomes with PpPD. DGE may be associated with weight loss and poornutritional status in long-term outcomes.