Clinical features and distribution of the APC variant in duodenal and ampullary polyps in patients with familial adenomatous polyposis: a multicenter retrospective cohort study in Japan.

BACKGROUND: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients. METHODS: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps. RESULTS: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants. CONCLUSIONS: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps.

Marital status after colorectal surgery in familial adenomatous polyposis: a nationwide multicenter study in Japan.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) experience psychological and social challenges concerning future events such as marriage and childbirth alongside the medical risks of colorectal cancer (CRC) and FAP-related disease. We retrospectively investigated the rate of marriage and childbirth postoperatively in Japanese patients with FAP. METHODS: We included 161 patients who had colorectal surgery and reported marital status from a national survey of 35 Japanese institutions. Participants were classified according to marital status: married before colectomy (80 patients), married after colectomy (13 patients), and unmarried (68 patients). RESULTS: The marriage rate for all 161 patients (57.8%, standardized ratio 0.95, 95% confidence interval [CI] 0.76-1.14) was comparable to that in the general Japanese population (57.1%). The marriage rate among the 81 patients who were unmarried before colectomy was low (16.0%); however, the standardized marital ratio (0.75, 95% CI 0.34-1.15) was not significantly lower than that of the general population. In multivariable logistic regression, younger age (born after 1980, odds ratio [OR] 0.12, p < 0.001) and genetic testing (OR 4.06, p = 0.001) were associated with postoperative marriage. Seventy-one percent of patients with FAP who married after colectomy became pregnant and achieved delivery. CONCLUSIONS: The marriage rate of patients with FAP was comparable to that of the general population whereas the rate after colectomy was low among patients with FAP. However, in patients with FAP, colorectal surgery itself may not lead to negative consequences in terms of fecundity.

Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

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.

Multicenter, single-arm, phase II study of the continuous use of panitumumab in combination with FOLFIRI after FOLFOX for RAS wild-type metastatic colorectal cancer: Exploratory sequential examination of acquired mutations in circulating cell-free DNA.

This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC). Additionally, clinical value of the RAS/BRAF mutation status in circulating cell-free DNA (ccfDNA) was evaluated; this evaluation was measured independently of the protocol treatment. Eligible patients with RAS wild-type mCRC who had received the first-line panitumumab plus FOLFOX treatment were recruited and administered continuous panitumumab combined with FOLFIRI. Progression-free survival (PFS) at 6 months was the primary endpoint, with threshold and expected values of 35% and 50%, respectively. In total, 54 patients were enrolled between October 2017 and October 2019. The crude 6-month PFS rate was 37.0%, with a 4.8-month median PFS. The response rate and disease control rate were 16.7% and 50.0%, respectively. Notably, of the 54 participants, 17 showed RAS/BRAF mutations until the end of the protocol treatment and of the 22 patients with progressive disease as their best response, 10 possessed RAS/BRAF mutations in their plasma ccfDNA at baseline. The median PFS significantly differed among patients harboring tumors with BRAF and RAS mutations and those with wild-type tumors. In conclusion, our study failed to show the expected efficacy of the continuous panitumumab use in the second-line treatment. Liquid biopsy discriminated the duration of PFS according to the mutation status. The effectiveness of continuous treatment with panitumumab should be evaluated in patients with RAS/BRAF wild-type mCRC determined by liquid biopsy at the start of the second-line treatment.

An advanced bipolar device helps reduce the rate of postoperative pancreatic fistula in laparoscopic gastrectomy for gastric cancer patients: a propensity score-matched analysis.

BACKGROUND: Advanced bipolar devices (ABD; e.g., LigaSure™) have a lower blade temperature than ultrasonically activated devices (USAD; e.g., Harmonic® and Sonicision™) during activation, potentially enabling accurate lymph node dissection with less risk of postoperative pancreatic fistula (POPF) due to pancreatic thermal injury in laparoscopic gastrectomy. Therefore, we compared the efficacy and safety of ABD and USAD in laparoscopic gastrectomy for gastric cancer patients. METHODS: A retrospective cohort study was conducted on patients who underwent laparoscopic distal gastrectomy (LDG) between August 2008 and September 2020. A total of 371 patients were enrolled, and short-term surgical outcomes, including the incidence of ISGPF grades B and C POPF, were compared between ABD and USAD. The risk factors for POPF in LDG were investigated by univariate and multivariate analyses. RESULTS: A propensity score-matching algorithm was used to select 120 patients for each group. The POPF rate was significantly lower (0.8 vs. 9.2%, p < 0.001), the morbidity rate was lower (13.3 vs. 28.3%, p < 0.001), the length of postoperative hospitalization was shorter (14 vs. 19 days, p < 0.001), and the lymph node retrieval rate was higher (34 vs. 26, p < 0.001) with an ABD than with a USAD. There were no mortalities in either group. A multivariate analysis showed that a USAD was the only independent risk factor with a considerably high odds ratio for the occurrence of POPF (USAD/ABD, odds ratio 8.38, p = 0.0466). CONCLUSION: An ABD may improve the safety of laparoscopic gastrectomy for gastric cancer patients.

Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.

BACKGROUND: Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. METHODS: We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. RESULTS: Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. CONCLUSION: Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

Efficacy and safety of regorafenib dose-escalation therapy for Japanese patients with refractory metastatic colorectal cancer (RECC study).

BACKGROUND: Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients. METHODS: Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933). RESULTS: 57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%). CONCLUSIONS: Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.

Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study.

BACKGROUND: Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site. METHODS: Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC. RESULTS: Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14-2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer). CONCLUSIONS: Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.

Repeated partial tissue bite with inadequate cooling time for an energy device may cause thermal injury.

BACKGROUND: Over the past three decades, the use of ultrasonically activated device (USAD) and advanced bipolar device (ABD) has grown in minimally invasive surgeries. However, the thermal profile differences during repeated dissection with different grasping ranges of energy devices, which provide valuable information for preventing thermal injury by energy devices, remain unclear. METHODS: We developed an ex vivo benchtop model to examine the temperature profile of the blade and jaws of two USADs (HARMONIC® ACE + and Sonicision™) and a ABD (Ligasure™ Maryland) with different grasping ranges (partial tissue and full tissue bite) in repeated dissection with minimum cooling time. The maximum temperature, time required for completion to dissection of 10 cm of porcine muscle, thermal spread, and cooling time to reach 60 °C were continuously measured using video thermography. In addition, to evaluate one more grasping range "no tissue", we performed a stress test that activated the USAD without tissue intervention to assess the effects of excessive load on the blade and jaw. RESULTS: Repeated dissection of energy devices with minimal cooling time results in high blade and jaw temperatures proportional to the incision distance. In particular, the USADs with partial tissue bite showed a significantly higher temperatures at the blade and jaw, longer cooling times, and higher lateral thermal spread than those with a full tissue bite and the ABD. The stress test with a USAD showed an extremely high blade temperature exceeding 400 °C, with the tissue pad melting only 13.2 s after activation. CONCLUSION: Although USAD with partial tissue bite help ensure precise dissection, repeated long activation with inadequate cooling time may increase the risk of thermal injury during surgery. These results suggest that surgeons should use energy devices properly while understanding the risks of adjacent organ damage that could result from abuse of the device.

iTriangular Stapling Technique: A Novel Reconstruction Method and Clinical Outcomes of Cervical Esophagogastric Anastomosis after Esophagectomy.

BACKGROUND: We herein report the feasibility and safety of cervical end-to-end anastomosis by the iTriangular stapling technique (iTST), which was developed as an extension of the triangular stapling technique (TST) after minimally invasive esophagectomy (MIE). METHODS: A total of 45 patients with thoracic esophageal cancer who underwent reconstruction with cervical esophagogastric anastomosis by iTST using a linear stapler after MIE between January 2016 and January 2019 were retrospectively reviewed. We modified and improved upon the TST by adding a 1- to 2-cm vertical incision on the anterior wall of the remnant esophageal stump to enlarge the anastomotic lumen and thereby reduce the risk of anastomotic stenosis. The short-term patient outcomes were determined to assess the safety and feasibility of our procedures. RESULTS: The median operating time was 686 (range, 319-1110) minutes, and the median blood loss was 170 (range, 5-1180) ml. There were no cases of anastomotic stenosis in this study, although 2 patients (4.4%) developed minor anastomotic leakage. A case (2.2%) of tracheal fistula due to the apex of the triangular anastomosis was resolved simply by delaying the patient's oral intake. The mean length of the hospitalization was 21 days. CONCLUSIONS: The iTST provides a larger lumen unlimited by the size of the esophagus in cervical esophagogastric anastomosis. This technique is feasible, and sufficient short-term results have been achieved. Further studies with the accumulation of more cases will be required to prove the benefits of iTST for reconstruction after MIE.

[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.

Metastatic Invasive Lobular Carcinoma of the Breast Presenting Peritoneal Metastasis with Bilateral Ureteral Obstruction.

The most common sites for recurrence of breast cancer are the lungs, liver, and bones. The frequency of peritoneal, gastrointestinal metastasis is significantly lower than those, and bilateral ureteral obstruction caused by peritoneal metastasis is relatively rare. A 66-year-old woman was referred to our hospital because of appetite loss and frequent urination. She was on adjuvant hormonal therapy for local recurrence of right breast cancer. She was diagnosed with bilateral ureteral obstruction due to extramural compression. Exploratory laparoscopy revealed omental cake and peritoneal nodules of which pathological examination showed peritoneal metastasis of invasive lobular carcinoma. Peritoneal metastases from breast cancer are unusual and consequently difficult to identify without non-invasive tools. Exploratory laparoscopy revealed that the cause of hydronephrosis in this case was peritoneal metastasis of invasive lobular carcinoma. Clinical history and histological study play a pivotal role in determining the correct diagnosis.

Overexpression of transmembrane protein 2 (TMEM2), a novel hyaluronidase, predicts poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: Abnormal metabolism of hyaluronan (HA), a major component of extracellular matrix, is a hallmark of cancer. Our previous studies have shown the importance of enzymes responsible for HA degradation in the aggressive phenotype of pancreatic ductal adenocarcinoma (PDAC). In the present study, we investigated the expression and function of transmembrane protein 2 (TMEM2), a recently identified HA-degrading enzyme, in PDAC. MATERIALS & METHODS: We used immunohistochemistry to investigate expression patterns of TMEM2 in archival tissues obtained from 100 patients with PDAC who underwent surgical resection from 1982 to 2012. The correlations between TMEM2 expression and clinicopathological variables, including survival, were determined using univariate and multivariate analyses. The effect of TMEM2 on proliferation and migratory ability (measured using transwell cell migration assay) of PDAC cells was determined by TMEM2 knockdown with small-interfering RNA (siRNA). RESULTS: Immunohistochemical analysis revealed high expression of TMEM2 in 22 (22%) of 100 patients. The overall survival was significantly shorter in patients with high TMEM2 expression than in those with low expression (P = 0.013). Multivariate analysis identified high TMEM2 expression as an independent factor predicting poor prognosis (P = 0.011). Unexpectedly, knockdown of TMEM2 resulted in increased migratory ability of PDAC cells, which was associated with increased expression of KIAA1199, a potent HA-degrading enzyme shown to enhance cell migration. CONCLUSION: TMEM2 overexpression is associated with poor prognosis in PDAC patients. Targeted disruption of this molecule, however, could enhance the aggressiveness of PDAC cells through a possible interaction with KIAA1199.

Clinical Outcomes of Laparoscopic Versus Laparotomic Distal Gastrectomy in Gastric Cancer Patients: A Multilevel Analysis Based on a Nationwide Administrative Database in Japan.

BACKGROUND: The present study compared the short-term outcomes and costs of laparoscopic distal gastrectomy (LDG) with those of open distal gastrectomy (ODG) for gastric cancer using a nationwide administrative database in Japan. METHOD: Overall, 37,752 patients with gastric cancer who underwent distal gastrectomy at 1074 hospitals in the fiscal year 2012-2013 were evaluated using a diagnosis procedure combination database in Japan. We performed a retrospective analysis via a multilevel analysis (MLA) of the short-term surgical results and costs of the LDG and ODG groups. The models included the age, sex, comorbid complications, smoking, body mass index (BMI), activity of daily living (ADL), stage, and the number of cases of gastrectomy per facility for adjustment. The in-hospital mortality relative to the hospital volume was also compared. RESULTS: The LDG group required postoperative blood transfusion less frequently and had fewer postoperative complications, shorter hospitalization, and lower operative mortality than the ODG group. While this stage did not correlate with the in-hospital mortality, the surgical method, age, sex, ADL, BMI, comorbidity, and yearly volume showed a correlation. A significant association in the in-hospital mortality was observed between low- and very-high-volume hospitals. CONCLUSION: In this large nationwide cohort of patients with gastric cancer using an MLA, LDG was shown to be safer with lower mortality and postoperative complication rates than ODG.

Open colectomy vs. laparoscopic colectomy in Japan: a retrospective study using real-world data from the diagnosis procedure combination database.

PURPOSE: To compare the short-term outcomes of conventional open colectomy with those of laparoscopic colectomy for colon cancer. METHODS: We retrieved data between January 2014 and March 2016 from the Diagnosis Procedure Combination database. A total of 69,418 patients who underwent colectomy for colon cancer were analyzed from among 15,901,766 cases of colorectal cancer. We applied a multilevel logistic regression model using a 2-level structure of individuals nested from 1065 hospitals. RESULTS: A total of 22,440 open colectomy and 46,978 laparoscopic colectomy procedures were performed. The in-hospital mortality rate was significantly lower in the laparoscopic group than in the open group (0.28% vs. 0.06%, odds ratio [OR] 0.40, p < 0.001). Similarly, the 30-day postoperative mortality rate (0.14% vs. 0.03%, OR 0.47, p = 0.019) and surgical morbidity rate (43.0% vs. 25.3%, OR 0.47, p < 0.001) were significantly lower in the laparoscopic group than in the open group. The postoperative length of stay was significantly longer in the open group (mean difference - 5.6 days, p < 0.001) than in the open group. The admission cost was significantly greater in the open group than in the laparoscopic group (mean difference - 95,080 yen, p < 0.001). CONCLUSIONS: Laparoscopic colectomy is safe and effective in the short term.

Robotic-Assisted Distal Gastrectomy for Gastric Cancer Using an Oval-Shaped Port Device.

INTRODUCTION: This report describes the techniques and outcomes of robot-assisted distal gastrectomy (RDG) for gastric carcinoma using an oval-shaped port device. MATERIALS AND METHODS: A total of 15 patients underwent RDG with lymphadenectomy using the E‧Z Access/LAP-PROTECTOR oval-type device (Hakko Co., Ltd., Tokyo, Japan) performed by a single surgeon between 2018 and 2019. This device was introduced to the umbilicus under two settings, depending on the patient's figure. A horizontal setting (n=7) was used to reduce the number of trocar skin incisions in thin patients by placing a scope trocar and assist port within the E-Z Access. The vertical setting (n=8) was used for large and obese patients, enabling the endoscope position to move 50mm toward the cephalad side by rotating the device 180° to improve the surgical view of the suprapancreatic area ("dual port position" using the E‧Z Access oval-type device). The intracorporeal Billroth-I anastomosis or Roux-en-Y method was used for reconstruction. The short-term patient outcomes were determined to assess the safety and feasibility of our procedures. RESULTS: The E-Z Access oval-type device was useful for maintaining an optimal surgical field and reducing the number of skin incisions and the level of surgeon stress. Furthermore, its removal cap and wound protector allowed for an airtight seal, umbilical wound protection, and smooth specimen removal and re-pneumoperitoneum. R0 resection was accomplished in all cases without the need for conversion to open or conventional laparoscopic surgery. The median operating time was 323 (range, 245-590) minutes, and the median blood loss was 5ml. The median number of retrieved lymph nodes was 30. Neither major postoperative complication, including umbilical skin damage, nor postoperative mortality, was observed. The mean length of the hospitalization was 12.5 days. CONCLUSIONS: Our robotic approach using an oval-shaped port device for gastric cancer patients is feasible in terms of patient safety and curability.

[A Case Report of Multiple Intussusceptions by Intestinal Metastases of Pleomorphic Carcinoma of the Lung].

A 68-year-old male with abdominal pain and vomiting was brought to our hospital by ambulance. Computed tomography showed multiple intussusceptions with pseudokidney signs in the jejunum and ileocecum, and a tumor of 5 cm in diameter in the left lower lobe of the lung. We performed an emergent operation, as a release of multiple intussusceptions was difficult by conservative treatment. There were two intussusceptions, in the jejunum and the ileocecum. We performed a partial resection of the jejunum and a resection of the ileocecum. Histopathological examination of the resected specimens and a biopsy specimen collected by bronchoscopy allowed us to diagnose multiple intussusceptions due to small intestine metastases from a pleomorphic carcinoma of the lung. This case is presented here, with a review of the literature.