Mechanical and oral antibiotics bowel preparation for elective rectal cancer surgery: A propensity score matching analysis using a nationwide inpatient database in Japan.

Aim: The best bowel preparation method for rectal surgery remains controversial. In this study we compared the efficacy and safety of mechanical bowel preparation (MBP) alone and MOABP (MBP combined with oral antibiotic bowel preparation [OABP]) for rectal cancer surgery. Methods: In this retrospective study we analyzed data from the Japanese Diagnosis Procedure Combination (DPC) database on 37 291 patients who had undergone low anterior resection for rectal cancer from 2014 to 2017. Propensity score matching analysis was used to compare postoperative outcomes between MBP alone and MOABP. Results: A total of 37 291 patients were divided into four groups: MBP alone: 77.7%, no bowel preparation (NBP): 16.9%, MOABP: 4.7%, and OABP alone: 0.7%. In propensity score matching analysis with 1756 pairs, anastomotic leakage (4.84% vs 7.86%, P < 0.001), small bowel obstruction (1.54% vs 3.08%, P = 0.002) and reoperation (3.76% vs 5.98%, P = 0.002) were less in the MOABP group than in the MBP group. The mean duration of postoperative antibiotics medication was shorter in the MOABP group (5.2 d vs 7.5 d, P < 0.001) than in the MBP group. There was no significant difference between the two groups in the incidence of Clostridium difficile (CD) colitis (0.40% vs 0.68%, P = 0.250) and methicillin-resistant Staphylococcus aureus (MRSA) colitis (0.11% vs 0.17%, P = 0.654). There was no significant difference in in-hospital mortality between the two groups (0.00% vs 0.11% respectively, P = 0.157). Conclusion: MOABP for rectal surgery is associated with a decreased incidence of postoperative complications without increasing the incidence of CD colitis and MRSA colitis.

The Effects of Hospital Volume on Short-Term Outcomes of Laparoscopic Surgery for Rectal Cancer: A Large-Scale Analysis of 37,821 Cases on a Nationwide Administrative Database.

INTRODUCTION: Laparoscopic low anterior resection (L-LAR) has become widely accepted for the treatment of rectal cancer. However, little is known about the superiority of L-LAR in a real-world setting (including low-volume hospitals) and the association between the short-term outcomes and hospital volume focusing on L-LAR. METHODS: This is a retrospective cohort study. A total of 37,821 patients who underwent LAR for rectal cancer were analyzed using the Diagnosis Procedure Combination (DPC) database from January 2014 to December 2017. The short-term surgical outcomes were analyzed using a multilevel analysis. Hospital volumes were divided into quartiles, including low (1-31), middle (32-55), high (56-91), and very-high volume (92-444 resections per 4 years). The effects of hospital volume on the outcomes were investigated. RESULTS: The study population included 8,335 patients (22%) who underwent open low anterior resection (O-LAR) and 29,486 patients (78%) who underwent L-LAR. The in-hospital mortality and morbidity were consistent with previous reports. In patients who underwent L-LAR, the in-hospital mortality (0.12% vs. 0.41%; OR: 0.33; p = 0.005), the rate of reoperation (3.76% vs. 6.48%; OR: 0.67; p < 0.001), and the perioperative transfusion rate (3.81% vs. 5.90%; OR: 0.66; p < 0.001) were significantly lower in very-high-volume hospitals than in low-volume hospitals. These effects of hospital volume were not observed in O-LAR. CONCLUSIONS: Our present study demonstrates that high volume improves outcomes in patients who underwent L-LAR in a real-world setting.

Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated hyaluronan metabolism. Our previous studies have shown increased expression of 2 newly identified hyaluronidases, KIAA1199 and transmembrane protein 2 (TMEM2), in PDAC. However, the relationship between these 2 hyaluronidases is unknown. In the present study, we investigated the correlation between KIAA1199 and TMEM2 expression in PDAC. METHODS: Using quantitative real-time reverse transcription polymerase chain reaction, we analyzed KIAA1199 and TMEM2 mRNA expression in 11 PDAC cell lines and frozen tissues from 12 patients with PDAC. We used immunohistochemistry to investigate expression patterns of KIAA1199 and TMEM2 in archival tissues obtained from 92 patients with PDAC who underwent surgical resection. We compared survival between 4 groups according to expression patterns of KIAA1199 and TMEM2. RESULTS: We found a significantly positive correlation between KIAA1199 and TMEM2 mRNA in PDAC cell lines and tissues. Immunohistochemical analysis found that median overall survival was 30.2 months in patients with low expression of KIAA1199 and TMEM2 and 12.5 months in those with high expression of both. Patients with high expression of KIAA1199 and TMEM2 had significantly shorter survival than other patient groups. CONCLUSIONS: Concurrent overexpression of these 2 hyaluronidases could be a strong prognostic marker in PDAC.

Prognostic and functional role of hyaluronan-binding protein 1 in pancreatic ductal adenocarcinoma.

Hyaluronan-binding protein 1 (HABP1) is among the molecules known to bind to hyaluronan and is involved in a variety of cellular processes, including cell proliferation and migration. HABP1 has been implicated in the progression of various cancers; however, there have been (to the best of our knowledge) few studies on the expression and function of HABP1 in pancreatic ductal adenocarcinoma (PDAC), a topic that is examined in the present study. Immunohistochemical analysis of HABP1 protein was conducted in archival tissues from 105 patients with PDAC. Furthermore, the functional effect of HABP1 on proliferation, colony formation, and migration in PDAC cells was examined by knockdown of HABP1. It was revealed that HABP1 was overexpressed in 49 (46.2%) out of 105 patients with PDAC. Overall survival was significantly shorter in patients with high HABP1 expression than in those with low HABP1 expression (median survival time of 12.8 months vs. 28.5 months; log-rank test, P=0.004). Knockdown of HABP1 expression in PDAC cells resulted in decreased cell proliferation, colony formation, and cell migration activity. Thus, HABP1 may serve as a prognostic factor in PDAC and may be of use as a novel therapeutic target.

Evaluation of cholecystectomy in older individuals using real-world data: a multilevel analysis based on a nationwide administrative database in Japan.

BACKGROUND: In the present study, we aimed to evaluate the clinical outcomes of cholecystectomy in older individuals. METHODS: In this retrospective study, data from the Japanese Diagnosis Procedure Combination database on 96,620 patients who had undergone cholecystectomy at 1060 hospitals from 2018 to 2020 were analyzed. Patients were divided into five age groups: < 75, 75-79, 80-84, 85-89, and ≥ 90 years. Associations between postoperative outcomes and age group were investigated by logistic regression analysis. Mean differences between age groups in time to postoperative recovery and cost were also compared. RESULTS: Older patients had higher rates of poor scores for activities of daily living and preoperative comorbidity. Compared with the youngest age group (< 75 years), the odds ratios for in-hospital mortality were 3.00 (95% confidence interval, 1.74-5.19), 7.54 (4.73-12.01), 13.47 (8.21-22.14), and 27.64 (15.56-49.09), in the 75-79, 80-84, 85-89, and ≥ 90-year-old age group, respectively (all p < 0.001). Furthermore, the length of postoperative hospital stay and rates of postoperative complications, postoperative reintubation, and reoperation with general anesthesia increased significantly in parallel with increasing age, the highest rates being in the ≥ 90 year-old age group. CONCLUSIONS: Our real-world data highlight the worse postoperative outcomes, including a higher mortality rate, in older patients undergoing cholecystectomy. Care should be taken when considering the indications for surgery in such patients.

Patient backgrounds and short-term outcomes of complicated appendicitis differ from those of uncomplicated appendicitis.

Background: Appendicitis is classified as either complicated (CA) or uncomplicated (UA). Some authors have shown that the epidemiologic trends of CA and UA may differ. The aim of this study was to clarify differences in backgrounds and surgical outcomes between CA and UA patients. Methods: This study was a cohort study. We extracted case data from the Japanese Diagnosis Procedure Combination (DPC) database from January 2014 to December 2017. Patients were classified into three groups, depending on whether they underwent emergency appendectomy for CA (CA group), emergency appendectomy for UA (UA group), or elective appendectomy (EA group). We evaluated patient characteristics and surgical outcomes for each group. Results: We included 89,355 adult patients in the study, comprising 29,331 CA, 48,691 UA, and 11,333 EA patients. Old age, larger body mass index, smoking, and medication with antidiabetic drugs, oral corticosteroids, oral antiplatelet drugs, and oral anticoagulant drugs were independent risk factors for CA. The percentage of CA increased with age. In-hospital mortality (0.15%, 0.02%, and 0.00%) and 30-d mortality (0.09%, 0.01%, and 0.00%), respectively, of CA patients were significantly higher than those of the UA and EA groups. The duration of postoperative antibiotic administration, duration of fasting, and time before removal of a prophylactic drain were significantly longer in the CA group than in the UA and EA groups. Conclusion: Backgrounds and treatment outcomes of CA and UA patients after emergency surgery are entirely different. Thus, the treatment strategy of CA and UA patients should differ accordingly.

Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterised by dense desmoplasia and hypoxic microenvironment. Our previous reports demonstrated that hyaluronan (HA), especially low-molecular-weight HA, provides a favourable microenvironment for PDAC progression. However, the effect of hypoxia on HA metabolism remains unknown. Using quantitative real-time RT-PCR and western blot analysis, we analysed the changes in the expression of HA-synthesizing enzymes (HAS2 and HAS3) and HA-degrading enzymes (HYAL1, KIAA1199/CEMIP) in PDAC cell lines under hypoxic conditions. Hypoxia increased the mRNA and protein expression of KIAA1199, whereas it decreased HYAL1 expression. The expression of HAS3 was increased and HAS2 remained unchanged in response to hypoxia. The effect of KIAA1199 on hypoxia-induced cell migration was determined using a transwell migration assay and small-interfering RNA (siRNA). Hypoxia enhanced the migratory ability of PDAC cells, which was inhibited by KIAA1199 knockdown. We also used immunohistochemistry to analyse the protein expression of hypoxia inducible factor (HIF) 1α and KIAA1199 in PDAC tissues. There was a significant immunohistochemically positive correlation between KIAA1199 and HIF1α. These findings suggest that hypoxia-induced KIAA1199 expression may contribute to enhanced motility in PDAC.

[A Case Report of Lateral Paracecal Hernia Treated with Single Port Surgery].

An 86-year-old female hospitalized for right femoral fracture complained of a sudden abdominal pain and vomited. Contrast-enhanced computed tomography (CECT) of the abdomen showed an ileal closed loop with dilatation of the oral side intestine. She was diagnosed with a bowel obstruction due to a paracecal hernia with incarceration and underwent an emergency operation. Under laparoscopy, the responsible ileum was incarcerated into the paracolic sulcus and strangulated. After releasing the strangulation by cutting the hernia hilum, the incarcerated ileum did not show any necrotic change. In this case, the CECT suggested paracecal hernia, showing the characteristic position between the cecum and the intestinal loop, which we successfully treated with a single incisional laparoscopic surgery.

A case of gallbladder adenocarcinoma arising in association with intracystic papillary neoplasm (ICPN) with abundant mucin production.

Intracystic papillary neoplasm (ICPN) of the gallbladder is a rare clinicopathological entity with a wide range of malignant potentials. Here, we report a case of mucin-producing gallbladder carcinoma possibly derived from ICPN. A 78-year-old female patient was referred to our hospital for examination of jaundice. Abdominal CT showed dilated biliary trees and a contrast-enhanced large polypoid mass in the gallbladder. Duodenoscopy showed a large amount of mucin extravasating from the ampulla of Vater. Bile cytology showed no evidence of malignancy. Under the diagnosis of mucin-producing gallbladder tumor, we performed laparoscopic cholecystectomy. Macroscopically, there was a large papillary tumor throughout the entire gallbladder mucosa. Pathological examinations showed a gallbladder adenocarcinoma localized to the mucosa in association with ICPN. Immunohistochemical analysis of the tumor revealed positive staining for MUC2 and MUC5AC but negative for MUC1 and MUC6, suggestive of the intestinal type.

Gallbladder metastasis of renal cell carcinoma presenting as a hypervascular polypoid lesion: case report of two cases with immunohistochemical analysis.

BACKGROUND: Metastasis of renal cell carcinoma (RCC) to the gallbladder is rare, and its clinicopathological feature remains poorly understood. We here present two cases of gallbladder metastasis from RCC presenting as a hypervascular polypoid lesion. CASE PRESENTATION: The first case was a 73-year-old man who had undergone right nephrectomy for clear cell RCC. Imaging studies detected a hypervascular polypoid lesion in the gallbladder 6 years after nephrectomy. Laparoscopic cholecystectomy was done. The pathological findings of the polypoid lesion showed proliferation of clear cells in the submucosal layer. Immunohistochemically, the tumor was positive for carbonic anhydrase 9 (CA9) but negative for cytokeratin 7 (CK7), suggestive of metastatic RCC. The second case was a 43-year-old man who had undergone right nephrectomy for clear cell RCC. Imaging studies revealed a hypervascular polypoid lesion of 20 mm in diameter in the gallbladder 1 year after nephrectomy. The patient underwent expanded cholecystectomy and extra-hepatic bile duct resection with lymphadenectomy. Microscopically, the polypoid lesion of the gallbladder was composed of clear cells in the submucosal layer. Immunohistochemical analysis showed positive staining for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) but negative staining for CK7, leading to the diagnosis of metastatic RCC. CONCLUSIONS: Gallbladder metastasis from RCC is rare but should be considered when a hypervascular polypoid lesion in the gallbladder is detected during the follow-up period after RCC treatment.

[A Case Report of Laparoscopy Assisted Distal Gastrectomy for Gastric Cancer with an Adachi Type VI Anomaly (Group 27)Institution].

We report the case of a 79-year-old man, with gastric cancer detected on upper gastrointestinal endoscopic examination performed by a nearby medical clinic, and referred to our hospital, in April 201X. He was diagnosed with gastric cancer(ML, less, 0- II a+ II c, tub 1-2, cT1bN0M0, cStage I A). We performed laparoscopy assisted distal gastrectomy, D1+lymph node dissection, and Billroth I (B- I )reconstruction. Abdominal CT scan before surgery confirmed vascular anomaly of the celiac artery. We diagnosed Adachi type VI, preserved hepato-gastric artery trunk, and performed D1 plus dissection plus B- I reconstruction with small incision in the epigastrium. The operation time was 244 minutes and the blood loss was 5 mL. There were no postoperative complications, and the patient was discharged from hospital 7 days after the surgery. Pathological findings revealed pT4aN0M0, pStage II B, and the patient has been treated with TS-1®postoperative adjuvant chemotherapy. At present, there is no recurrence. As vascular anomalies of the celiac artery branch exhibit various forms, occasional blood vessel preventing surgery is required. Examining blood vessels through CT scan before the surgery made it possible to perform Laparoscopic gastrectomy safely.

Golimumab monotherapy in Japanese patients with active rheumatoid arthritis despite prior treatment with disease-modifying antirheumatic drugs: results of the phase 2/3, multicentre, randomised, double-blind, placebo-controlled GO-MONO study through 24 weeks.

OBJECTIVE: To evaluate the efficacy and safety of golimumab 50 and 100 mg monotherapy in Japanese patients with active rheumatoid arthritis (RA) despite treatment with disease-modifying antirheumatic drugs (DMARDs). METHODS: A total of 316 patients were randomised to receive subcutaneous injections every 4 weeks of placebo (group 1), golimumab 50 mg (group 2) or golimumab 100 mg (group 3); group 1 crossed over to golimumab 50 mg at week 16. The primary end point was the proportion of patients achieving ≥20% improvement in the American College of Rheumatology criteria (ACR20) at week 14. ACR50 and ACR70 response rates were also measured. Adverse events (AEs) were monitored throughout the study. RESULTS: Demographics were similar across groups; the mean age was 52 years and 81.8% of patients (252/308) were female. Week 14 ACR20 response rates were significantly greater in groups 2 (51/101 (50.5%)) and 3 (60/102 (58.8%)) than in group 1 (20/105 (19.0%); p<0.0001 for both), as were ACR50 and ACR70 response rates. After placebo crossover at week 16, week 24 ACR response rates were similar in groups 1 and 2. Through week 16, 63.8% of patients in group 1, 62.4% in group 2 and 60.8% in group 3 had AEs and 1.9%, 1.0% and 2.0% had serious AEs. After week 16, one malignancy was reported (breast cancer, group 3). Infections were the most common AEs. No deaths or cases of tuberculosis were reported through week 24. CONCLUSIONS: Golimumab monotherapy (50 and 100 mg) was effective in reducing the signs and symptoms of RA in Japanese patients with active disease despite DMARD treatment.

Golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis: results of the GO-FORTH study.

OBJECTIVE: To assess the efficacy and safety of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). METHODS: 269 Japanese patients with active RA despite treatment with MTX were randomised (1:1:1) to placebo + MTX (Group 1), golimumab 50 mg + MTX (Group 2) or golimumab 100 mg + MTX (Group 3). Subcutaneous golimumab/placebo was injected every 4 weeks; stable doses of oral MTX (6-8 mg/week) were continued. Patients were allowed to enter early escape (Group 1 added golimumab 50 mg, Group 2 increased golimumab to 100 mg, Group 3 continued golimumab 100 mg) based on swollen/tender joint counts at week 14. The primary study endpoint was achievement of at least 20% improvement in the American College of Rheumatology (ACR20) response criteria at week 14. To control for multiplicity of testing, treatment group comparisons were first made between combined Groups 2 and 3 versus Group 1, followed by comparisons of Group 2 and Group 3 versus Group 1. RESULTS: The proportion of patients with an ACR20 response at week 14 was significantly higher in combined Groups 2 and 3 (73.4%, 127/173) and in each of Group 2 (72.1%, 62/86) and Group 3 (74.7%, 65/87) compared with Group 1 (27.3%, 24/88; p<0.0001 for all comparisons). Golimumab + MTX also elicited a significantly better response than placebo + MTX in other efficacy parameters, including disease activity score (DAS28) response/remission and radiographic assessments. During the 16-week fixed treatment regimen study period, 72.7%, 75.6% and 78.2% of patients had adverse events and 1.1%, 1.2% and 2.3% had serious adverse events in Groups 1, 2 and 3, respectively. CONCLUSION: In Japanese patients with active RA despite MTX therapy, golimumab + MTX was significantly more effective than MTX monotherapy in reducing RA signs/symptoms and limiting radiographic progression with no unexpected safety concerns.