Efficacy of Pancreatic Dissection With a Triple-row Stapler in Laparoscopic Distal Pancreatectomy: A Retrospective Observational Study.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) occur after 20% to 30% of laparoscopic distal pancreatectomies. This study aimed to evaluate the clinical efficacy of laparoscopic distal pancreatectomy using triple-row staplers in preventing POPFs. METHODS: Between April 2016 and May 2023, 59 patients underwent complete laparoscopic distal pancreatectomies. There were more females (n=34, 57.6%) than males (n=25, 42.4%). The median age of the patients was 68.9 years. The patients were divided into slow-compression (n=19) and no-compression (n=40) groups and examined for pancreatic leakage. Both groups were examined with respect to age, sex, body mass index (BMI), pancreatic thickness at the pancreatic dissection site, pancreatic texture, diagnosis, operative time, blood loss, presence of POPF, date of drain removal, and length of hospital stay. In addition, risk factors for POPF were examined in a multivariate analysis. RESULTS: Grade B POPFs were found in 9 patients (15.3%). Using univariate analysis, the operative time, blood loss, postoperative pancreatic fluid leakage, day of drain removal, and hospital stay were shorter in the no-compression group than in the slow-compression group. Using multivariate analysis, the absence of POPFs was significantly more frequent in the no-compression group (odds ratio, 5.69; 95% CI, 1.241-26.109; P=0.025). The no-compression pancreatic dissection method was a simple method for reducing POPF incidence. CONCLUSIONS: The method of quickly dissecting the pancreas without compression yielded better results than the method of slowly dissecting the pancreas with slow compression. This quick dissection without compression was a simple and safe method that minimized postoperative pancreatic fluid leakage, shortened the operative time and length of hospital stay, and reduced medical costs. Therefore, this method might be a clinically successful option.

The association between surgical site infection and postoperative colorectal cancer recurrence and the effect of laparoscopic surgery on prognosis.

PURPOSE: Studies have shown that surgical site infection (SSI) incidence is lower in patients undergoing laparoscopic surgery. Therefore, we reported the SSI countermeasures adopted by our institution and aimed to evaluate the association between SSI occurrence and postoperative colorectal cancer recurrence and the usefulness of laparoscopic surgery for prognosis. METHODS: Among the patients with colorectal cancer who underwent radical surgery at our hospital between January 2015 and December 2017, 197 with stage I-III cancer without distant metastases were included. We retrospectively analyzed patients' electronic medical records and classified them into the non-SSI (without SSI, n = 159) and SSI (with SSI, n = 38) groups. We calculated and compared the 5-year relapse-free survival (RFS) and overall survival (OS) rates. Additionally, we assessed the relationship between prognosis in the non-SSI, incisional SSI, and organ/space SSI groups and the usefulness of laparoscopic surgery. RESULTS: The 5-year RFS and OS were 80.5% versus 63.2% (P = 0.024; hazard ratio [HR], 2.065; 95% confidence interval [CI], 1.099-3.883) and 88.7% versus 84.2% (P = 0.443; HR, 1.436; 95% CI, 0.570-3.617), respectively. The SSI group had a significantly worse 5-year RFS prognosis. Regarding the relationship with laparoscopic surgery, the SSI incidence was 45.0% (9/20 cases) and 16.4% (29/177 cases) with laparotomy and laparoscopic surgery, respectively, indicating a significantly reduced SSI occurrence with laparoscopic surgery (P = 0.005). CONCLUSION: Patients with SSI were at high risk for colorectal cancer recurrence, and laparoscopic surgery may be useful for reducing SSI.

Subserosal Layer and/or Pancreatic Invasion Based on Anatomical Features as a Novel Prognostic Indicator in Patients with Distal Cholangiocarcinoma.

The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.

Endovascular treatment of postoperative hemorrhage after pancreatectomy: a retrospective study.

BACKGROUND: Ruptured aneurysm is a serious complication of distal pancreatectomy (DP) or pancreatoduodenectomy (PD) that can be life-threatening if not treated promptly. This study aimed to examine the efficacy of a Viabahn stent graft for stopping bleeding after pancreatectomy. METHODS: Between April 2016 and June 2022, we performed 245 pancreatectomies in our institution. Six patients experienced postoperative bleeding and underwent endovascular treatment. RESULTS: All six cases of bleeding occurred post-PD (3.7%). The bleeding was from gastroduodenal artery (GDA) pseudoaneurysms in three patients, and Viabahn stent grafts were inserted. All three patients did not show liver function abnormalities or hepatic blood flow disorders. One patient with a Viabahn stent graft experienced rebleeding, which required further management to obtain hemostasis. Of the six cases in which there was hemorrhage, one case of bleeding from the native hepatic artery could not be managed. CONCLUSIONS: Using the Viabahn stent graft is an effective treatment option for postoperative bleeding from GDA pseudoaneurysms following PD. In most cases, using this device resulted in successful hemostasis, without observed abnormalities in hepatic function or blood flow.

Factors contributing to nonalcoholic fatty liver disease (NAFLD) and fat deposition after pancreaticoduodenectomy: A retrospective analysis.

Aim: Nonalcoholic fatty liver disease (NAFLD) can occur due to various reasons after pancreaticoduodenectomy (PD). This study examined the risk and perioperative determinants of NAFLD and fat deposition after PD. Methods: A total of 101 patients who had undergone computed tomography 6 months after PD were included. We compared perioperative factors between patients who developed NAFLD and those who developed fatty deposits after PD. Results: In the NAFLD group, pancreatic cancer was significantly more prevalent among patients who developed postoperative NAFLD (p = 0.024) and had a lower postoperative body mass index (BMI; p = 0.008). Multivariate analysis revealed that pancreatic carcinoma (hazard ratio [HR] 4.42, 95% confidence interval [CI] 1.118-17.442, p = 0.034) and lower postoperative BMI (HR 0.51, 95% CI 0.274-0.954, p = 0.0355) were risk factors for fatty liver. Pancreatic leakage (p = 0.024) and postoperative BMI (p = 0.002) were significantly lower in the fat deposition group than those in the NAFLD group. Multivariate analysis also revealed that a lower postoperative BMI was a risk factor for fat deposition (HR 0.56, 95% CI 0.523-0.982, p = 0.042). Moreover, multivariate analysis revealed that the fat deposition group had significantly lower pancreatic leakage than the NAFLD group (HR 7.944, 95% CI 1.993-63.562, p = 0.049). Conclusion: The findings of this study suggest that postoperative BMI and pancreatic cancer are associated with a higher risk of NAFLD after PD, possibly because of pancreatic exocrine insufficiency and impaired fat absorption.

Sensitivity of endoscopic ultrasound-guided fine-needle aspiration cytology and biopsy for a diagnosis of pancreatic ductal adenocarcinoma: A comparative analysis.

The utility of endoscopic ultrasound fine-needle aspiration cytology (EUS-FNAC) or endoscopic ultrasound fine-needle aspiration biopsy (EUS-FNAB) for diagnosis of small and large pancreatic ductal adenocarcinomas (PDACs) remains in question. We addressed this by analyzing 97 definitively diagnosed cases of PDAC, for which both EUS-FNAC and EUS-FNAB had been performed. We subclassified the 97 solid masses into small (n = 35) or large (n = 62) according to the maximum tumor diameter (<24 mm or ≥24 mm) and compared the diagnostic sensitivity (truly positive rate) of EUS-FNAC and of EUS-FNAB for small and large masses. Diagnostic sensitivity of EUS-FNAC did not differ between large and small masses (79.0% vs. 60.0%; p = 0.0763). However, the diagnostic sensitivity of EUS-FNAB was significantly higher for large masses (85.5% vs. 62.9%; p = 0.0213). Accurate EUS-FNAC-based diagnosis appeared to depend on the degree of cytological atypia of cancer cells, which was not associated with quantity of cancer cells. The accuracy of EUS-FNAB-based diagnosis appeared to depend on cancer cell viability in large masses and cancer volume in small masses. Based on the advantages or disadvantages in each modality, both modalities play an important role in the qualitative diagnosis of PDAC as a complementary procedure.

A single-center retrospective analysis of the efficacy and safety of a modified regimen of irinotecan plus S-1 (IRIS) with molecular targeting agents as second-line chemotherapy in Japanese patients with recurrent or nonresectable colorectal cancer.

Background: As the second-line chemotherapy for stage IV recurrent or nonresectable colorectal cancer, our hospital started a modified treatment regimen comprising of irinotecan plus S-1 (IRIS) [tegafur/gimeracil/oteracil (S-1)] plus molecular targeting agents (MTAs), i.e., an epidermal growth factor receptor (EGFR) inhibitor such as panitumumab (P-mab) or cetuximab (C-mab) or vascular endothelial growth factor (VEGF) inhibitor such as bevacizumab (B-mab) since October 2012. The purpose of this study is to evaluate the efficacy and safety of this modified regimen. Methods: This retrospective study included 41 patients with advanced recurrent colorectal cancer at our hospital whom at least 3 courses of chemotherapy were conducted from January 2015 to December 2021. Based on the location of the primary tumor, patients were classified into two group (right-sided group, proximal to the splenic curve, and left-sided, distal to the splenic curve). We assessed archived data on RAS and BRAF status and UGT1A1 polymorphisms and use of the VEGF inhibitor bevacizumab (B-mab) and the EGFR inhibitors panitumumab (P-mab) and cetuximab (C-mab). In addition, progression-free survival rate (36M-PFS) and the overall survival rate (36M-OS) were calculated. Furthermore, the respective median survival time (MST), the median number of treatment courses; the objective response rate (ORR) and clinical benefit rate (CBR) and the incidence of adverse events (AEs) were assessed as well. Results: There were 11 patients (26.8%) in the right-sided group, and 30 patients (73.2%) in the left-sided group. There were 19 patients with RAS wild type (46.3%) (1 in the right sided group and 18 in the left sided group). P-mab was used for 16 of these patients (84.2%), C-mab for 2 (10.5%), and B-mab for 1 (5.3%); the remaining 22 patients (53.7%). Ten patients in the right group and 12 patients in the left group were a mutated type and received B-mab. BRAF testing was performed in 17 patients (41.5%); as more than 50% of patients (58.5%) were included before the assay's introduction. Five patients in the right-sided group and 12 patients in the left-sided group had wild type. There was no mutated type. UGT1A1 polymorphism was tested in 16/41 patients: Eight were wild type (8/41 patients, 19.5%) and 8, mutated type. Regarding the *6/*28 double heterozygous type, there was only 1 patient in the right-sided group and the remaining 7 patients were in the left-sided group. The total number of chemotherapy courses was 299, and the median number, 6.0 (range, 3-20). PFS, OS, and MST were as follows: 36M-PFS (total/Rt/Lt), 6.2%/0.0%/8.5% (MST; 7.6/6.3/8.9 months); and 36M-OS (total/Rt/Lt), 32.1%/0.0%/44.0% (MST; 22.1/18.8/28.6 months). The ORR and CBR were 24.4% and 75.6%, respectively. The majority of AEs were grades 1 or 2 and were improved with conservative treatment. Grade 3 leukopenia was observed in 2 cases (4.9%), neutropenia in 4 cases (9.8%), and malaise/nausea/diarrhea/perforation in 1 case each (2.4%). Grade 3 leukopenia (2 patients) and neutropenia (3 patients) were more commonly observed in the left-sided group. Diarrhea and perforation were also common in the left-sided group. Conclusions: This second-line modified IRIS regimen with MTAs is safe and effective and results in good PFS and OS.

Gradual increase of avacopan dose with concomitant ursodeoxycholic acid use may help avoid the risk of C5a receptor inhibitor-induced liver injury in antineutrophil cytoplasmic antibody-associated vasculitis.

Microscopic polyangiitis is a necrotising vasculitis characterised by anti-neutrophil cytoplasmic antibodies against myeloperoxidase. The complement component 5a receptor inhibitor avacopan effectively sustains remission in microscopic polyangiitis with a reduction in prednisolone dosage. Liver damage is a safety concern for this drug. However, when it occurs and how to treat it remain unknown. A 75-year-old man developed microscopic polyangiitis and presented with hearing impairment and proteinuria. Methylprednisolone pulse therapy followed by 30 mg/day prednisolone and two doses of weekly rituximab were administered. Avacopan was initiated to taper prednisolone for sustained remission. After 9 weeks, liver dysfunction and sparse skin eruptions developed. The cessation of avacopan and the initiation of ursodeoxycholic acid improved liver function without discontinuation of prednisolone and other concomitant drugs. After 3 weeks, avacopan was rechallenged with a small dose that was gradually increased; ursodeoxycholic acid was continued. Full-dose avacopan did not induce recurrence of liver injury. Therefore, gradually increasing the dose of avacopan with concomitant ursodeoxycholic acid use may help avoid possible avacopan-induced liver injury.

Functional evaluations comparing Billroth I with a large remnant stomach and Roux en Y with a small remnant stomach following laparoscopic distal gastrectomy for gastric cancer: An investigation including laparoscopic total gastrectomy.

PURPOSE: This study compared the pros and cons of two post-distal gastrectomy (DG) reconstruction methods by comparing the patient quality of life and functional dynamics at one year postoperatively. METHODS: We compared functional outcomes between Billroth I following laparoscopic 1/2 DG (L-B1; n = 27) and Roux en Y following laparoscopic 4/5 DG (L-RY; n = 24), including laparoscopic total gastrectomy (L-TG; n = 25), at one year postoperatively. Clinical investigations were performed in each patient, and functional evaluations by the acetaminophen (AAP) absorption test and plasma gastrointestinal hormone measurements were performed in consenting patients in each group (L-B1: n = 10, L-RY: n = 10, L-TG: n = 5). RESULTS: Postoperative/preoperative body weight ratios were significantly higher in the L-B1 and L-RY groups, in descending order than the L-TG group, although the meal intake ratio was not significantly different between the L-B1 and L-RY groups. The incidence of remnant gastritis was significantly higher in the B1 than in the RY group. AAP levels, glucose and glucagon-like peptide 1 were significantly lower in the L-B1 than in the L-RY group. Active ghrelin levels (AGL) were similar between the L-B1 and L-RY groups. CONCLUSIONS: L-B1 maintains gradual intestinal absorption and physiological meal passage and prevents postoperative weight loss. L-RY results in maintenance of the postoperative meal intake via high AGL, equivalent to that in the L-B1 group.

Conversion surgery by hand-assisted laparoscopic surgery following chemotherapy for rectal cancer with H3 liver metastases: a case report.

Background: Recent advancements in molecularly targeted chemotherapy for stage IV colorectal cancer have enabled the possibility of complete resection in primary colorectal cancer, which often involves distant liver or lung metastases, by aggressive surgical resection followed by multi-combination chemotherapy. Case description: A 73-year-old man treated previously for hyperuricemia, hypertension, and a dissecting abdominal aortic aneurysm was referred to us after an incidental finding of multiple liver masses on abdominal ultrasound during follow-up for the aneurysm. A detailed examination by contrast-enhanced computed tomography revealed a ring-enhancing mass larger than 5 cm in diameter in segment 3 of the liver and more than 6 low-density areas with total diameter of 1 to 2 cm in both lobes. A barium enema examination revealed a Borrmann type 2 lesion covering two-thirds of the circumference of the colon, with a 5-cm major axis in the rectosigmoid colon. Biopsy revealed a well-differentiated adenocarcinoma. The patient was diagnosed with stage IV rectal cancer. Because there was no intestinal obstruction, we administered 9 cycles of bevacizumab with capecitabine and oxaliplatin as chemotherapy. Subsequent diagnostic imaging revealed the metastatic lesions in liver segment 3 had reduced to 2 low-density areas with a diameter of 8 mm, and the other hepatic metastases had disappeared; the main tumor had flattened and shrunk. Therefore, we used hand-assisted laparoscopic surgery (HALS) to perform anterior resection of the rectosigmoid colon and partial resection of liver segment 3 as conversion therapy. The patient was discharged 10 days after surgery. The rectal lesion was a well-differentiated adenocarcinoma with a depth of invasion of p-MP and a spread of L0, V0, and pN0. The partial hepatectomy did not indicate viable cancer cells; only necrotic, lysed tissue was observed. Postoperative chemotherapy involved 4 cycles of bevacizumab with capecitabine and oxaliplatin. At more than 42 months postoperatively, no metastasis or recurrence has been observed. Conclusions: This rare case demonstrates that conversion surgery can be a viable option following systemic chemotherapy in patients with advanced colon cancer and H3 liver metastases.

Development of Surgical System Using Bellows-Type Foldable Five-Fingered Robot Hand Inserted through a 20-mm Port.

The purpose of this study was to develop a robotic hand to assist with large organs, instead of using a surgeon, in laparoscopic surgery. Grasping, pinching, and exclusion were performed by three subjects with no medical knowledge. The results indicate that the proposed system can perform surgical operations in hand-assisted laparoscopic surgery when the subjects are proficient. However, the thumb mechanism and the wrist control method were required improvement because it was difficult to approach organs. Surgeons were asked to operate the robotic hand while watching the laparoscope image, and they were able to grasp and pinch with little practice.

A 73-Year-Old Woman Treated for Rheumatoid Arthritis with Lower Rectal Carcinoma Who Underwent Abdominoperineal Resection, Lateral Regional Lymph Node Resection, and Partial Hepatectomy by Hand-Assisted Laparoscopic Surgery (HALS): A Case Report.

BACKGROUND This report describes the case of a 73-year-old woman treated for rheumatoid arthritis with lower rectal carcinoma who underwent abdominoperineal resection, lateral regional lymph node resection, and partial hepatectomy by hand-assisted laparoscopic surgery (HALS). More recently, HALS has proven to be useful in multiple organ resections. CASE REPORT A 73-year-old woman who presented with hematochezia was diagnosed with lower rectal cancer and referred to our hospital. The patient had a history of rheumatoid arthritis and was taking oral nonsteroidal anti-inflammatory drugs. After further evaluation, the patient was diagnosed with stage IV rectal cancer with a metastatic liver lesion and a right lateral lymph node metastasis. All lesions were resected using HALS. A 50-mm longitudinal umbilical incision was created for use as a hand access site, and 3 ports with a diameter of 5 mm each were inserted into the lower abdomen to perform right lateral lymph node dissection and abdominoperineal resection. HALS was performed in the upper abdomen, where the liver was used to partially resect segment S6. The patient was discharged without complications 13 days after the operation. CONCLUSIONS In this complex case of advanced rectal carcinoma with liver metastases, use of the HALS surgical method was shown to be possible. Immunomodulatory treatment for rheumatoid arthritis may have influenced the outcome for this patient.

Efficacy of hand-assisted laparoscopic surgery (HALS) in older adult patients (≥80 years) with primary colorectal cancer.

Background: From 2004 to 2014, 821 colorectal cancer primary resections were conducted at our institution. Of these, 102 patients (12.4%) were older adults over 80 years old. underwent either the conventional laparotomy group (72 patients) or the hand-assisted laparoscopic surgery (HALS) group (30 patients). Methods: Data were extracted for 102 patients over 80 years old who underwent primary resection for colorectal cancer and were divided into two groups: conventional laparotomy (CL) (n=72) and hand-assisted laparoscopy (n=30). Pre-operative characteristics and outcomes were compared. Results: Baseline characteristics were similar between groups, except for age: CL group median 83.5 years old (range, 80-92 years old) and hand-assisted laparoscopy (HALS) group median 81.5 years old (range, 80-88 years old) (P=0.027). Pre-operative cardiac and lung function risk, performance status, and pathological classification stage (pStage) were almost similar between groups (P=0.668, P=0.176, P>0.999, P=0.217). No significant differences were found for operation time. The HALS group resulted in less blood loss (median 204 mL in the CL group and median 68 mL in the HALS group, P=0.003), shorter postoperative hospital stay (median was 18 days in the CL group and median was 12 days in the HALS group, P<0.001), and fewer postoperative wound infections (18 cases in the CL group and 2 cases in the HALS group, P=0.034). Five-year relapse-free survival (5Y-RFS) was 48.1% in the CL group and 73.3% in the HALS group (P=0.028). Five-year overall survival (5Y-OS) was 48.2% in the CL group and 73.3% in the HALS group (P=0.027). Conclusions: Approximately 70% of surgical treatment for patients over 80 years old with colorectal carcinoma were performed by CL. However, HALS had significant advantages including less blood loss, fewer wound infections, and shorter hospital stays. Therefore, HALS could proactively be considered to older adult patients with colorectal cancer.

Fibrin glue injection method for complex fistula after laparoscopic distal pancreatectomy: a case report.

BACKGROUND: Pancreatic fistula is the most problematic complication in pancreatectomy. Although drainage can be used to relieve this complication, pancreatic surgeons often encounter refractory pancreatic fistula. Fibrin glue injection, with the use of a twofold diluted solution B and a double-lumen tube, was found effective in treating this complicated pancreatic fistula. CASE PRESENTATION: We report the case of a 64-year-old Japanese man who underwent laparoscopic distal pancreatectomy for pancreatic tail cancer. After initial drainage of the pancreatic fistula diagnosed 4 days postoperatively, on day 134, refractory pancreatic fistula was observed using contrast-enhanced computed tomography. We used fibrin glue injection, with a twofold diluted solution containing thrombin and calcium chloride and a double-lumen tube, for treating the refractory fistula; the fluid drainage was almost stopped with no fever or abdominal pain. No recurrence of pancreatic cancer has been observed since the procedure. CONCLUSIONS: Fibrin glue injection was effective for complicated pancreatic fistula after distal pancreatectomy. Using a twofold diluted solution B containing thrombin and calcium chloride and a double-lumen tube makes possible the thorough injection of fibrin glue.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.

Scatter patterns in lymph node metastases as a novel prognostic indicator in patients with stage III/N2 colorectal cancer.

To classify patients with stage III/N2 colorectal cancer into high- and low-risk groups for recurrence, the present study compared clinicopathological features by immunohistochemical staining. The single-center analysis included 53/668 patients (7.9%) with stage III/N2 colorectal cancer who underwent radical resection between January 2006 and December 2014. The present study examined cancer cell distribution in metastatic lymph nodes and classified patients into a group with circumferential localization patterns like a cystic mass (CLP) and a group with scatter patterns like fireworks (SPF). Subsequently, 5-year relapse-free survival (5Y-RFS) and 5-year overall survival (5Y-OS) rates were compared and the histological type (differentiation degree) of the primary adenocarcinoma was included. The CLP group included 16 patients (30.2%) and the SPF group included 37 patients (69.8%). The 5Y-RFS rates in these groups were 75.0 vs. 37.8%, respectively (P=0.021), and the 5Y-OS rates were 81.3 vs. 48.6% (P=0.033). Patient clinicopathological characteristics exhibited no significant differences between groups. The adenocarcinoma was well differentiated in 14 patients (Well; 26.4%) and moderately (Mod; n=37) or poorly (Por; n=2) differentiated in 39 patients (Mod+Por; 73.6%). Patients were further classified into four groups: Well/CLP (n=6), Well/SPF (n=8), Mod+Por/CLP (n=10) and Mod+Por/SPF (n=29). For Well/CLP vs. Well/SPF, the 5Y-RFS rates were 66.7 vs. 25.0%, respectively (P=0.293), and for Mod+Por/CLP vs. Mod+Por/SPF (80.0 vs. 41.4%; P=0.052), the respective values for 5Y-OS were 66.7 vs. 50.0% (P=0.552) and 90.0 vs. 48.3% (P=0.059). Based on the aforementioned results, the CLP group was considered a low-risk group for recurrence with a relatively good prognosis; however, the SPF group was considered a high-risk group for recurrence with a poor prognosis, suggesting a need for more potent multi-combination chemotherapy in these patients from the early postoperative period.

A patient with paraganglioma undergoing laparoscopic resection: A case report.

Paraganglioma is a very rare extraadrenal nonepithelial tumor. The number of cases of laparoscopic surgery in Paraganglioma is small and controversial. This study encountered a case of successful transperitoneal laparoscopic surgery for a 56-mm paraganglioma in a 53-year-old female. Moreover, previous reports on laparoscopic surgery for paraganglioma are reviewed.

Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with stage IV recurrent or non-resectable colorectal cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been conducted for patients with non-resectable colorectal cancer; however, few reports of a systematic approach to NAC exist. At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX) has been used as chemotherapy for Stage IV colorectal cancer since 2014. We aimed to evaluate the efficacy and safety of NAC with a molecular-targeting agent for Stage IV colorectal cancer. METHODS: A retrospective, single-institute analysis was performed including 27 patients with advanced recurrent cancer following primary tumor resection and 43 patients with non-resectable tumors and remote metastasis. At the time of resection, 17 were receiving chemotherapy. All 70 patients received at least 3 cycles of B-mab XELOX (total: 920 cycles). We determined the 1-year progression-free survival (1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of treatment cycles. The objective response rate, clinical benefit rate, and adverse events were assessed. The number of chemotherapy cycles, survival time, and R0 surgery rate were determined for patients who underwent RO conversion surgery. RESULTS: The 1Y-PFS was 28.5% [median survival time (MST): 7.4 months], 1Y-OS was 76.6% (MST not reached), 3Y-PFS was 5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively. The objective response rate was 28.6%, and the clinical benefit rate was 58.6%. Grade 1 or Grade 2 adverse events occurred in 60 patients (85.7%); however, they all resolved without intervention. A single Grade 4 event (perforation of the primary tumor) occurred in 1 patient (1.4%). RO conversion surgery was performed in 7 patients (10.0%; primary + liver in 2 patients, primary + lung in 1 patient, liver in 3 patients, and primary in 1 patient). These patients received 3 to 10 cycles preoperatively (mean: 7.3; median: 6.5). R0 surgery was achieved in 5 of the 7 patients (71.4%). Postoperative survival ranged from 1 to 26 months (MST: 8 months). CONCLUSIONS: This modified regimen was safe and effective in Japanese patients, and a high quality of life/quality-adjusted life-year was achieved. To further evaluate PFS and OS, more patients are being investigated.

Autopsy of a case of rheumatoid arthritis with severe bicytopoenia due to gelatinous transformation of the bone marrow.

We present the case of an elderly female patient with rheumatoid arthritis (RA) treated with methotrexate. She was referred to our hospital with severe malaise. She was emaciated and had massive pleural effusion that induced atelectasis. Her blood tests revealed elevated CRP, leukopenia, and severe anaemia. She lost consciousness on the third day of hospital stay and passed away the following day. Her autopsy showed gelatinous transformation of the bone marrow that gave rise to bicytopoenia, whereas there were no other causes for severe anaemia. Bone marrow gelatinous transformation can cause impaired haematopoiesis in elderly RA patients.