Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Manipulation and Visualization of Peroxisomes in Drosophila.

Drosophila melanogaster is a proven metazoan model to investigate the fundamentals of human genetic diseases including peroxisome-related disorders. Drosophila have facile cell and animal culture but with a relatively simpler genome and organ morphology compared to vertebrates. Drosophila Schneider 2 (S2) cells have been used extensively as a platform for investigating peroxisome functions like transport along the cytoskeleton via their amenability to RNA-interference (RNAi)-based gene knockdown. Similarly, novel findings regarding tissue-specific roles for peroxisomes have come from studies in developing flies. Individual organs can be targeted for RNAi or gene mutations affecting a limited group of cells in the context of the entire animal. Here, we provide basic protocols on how to visualize peroxisomes and manipulate expression of the Peroxin or other peroxisome genes in S2 cells and developing Drosophila organs.

Lymphatic flow mapping during colon cancer surgery using indocyanine green fluorescence imaging.

With the development of surgical technology, indocyanine green (ICG) fluorescence navigation systems may be useful in various areas of colorectal surgery, including tumor location confirmation, bowel perfusion, ureter identification, and lymph node mapping. This review provides an overview of the current status of ICG-based navigation surgery in colorectal surgery, emphasizing its role in lymphatic flow mapping. This state-of-the-art approach will allow for appropriate oncological surgeries in the field of colorectal cancer and improve the patient's prognosis.

The usefulness of the endoscopic surgical skill qualification system in laparoscopic right hemicolectomy: a single-center, retrospective analysis with propensity score matching.

PURPOSE: Recently, a new certification system called the Endoscopic Surgical Skill Qualification System (ESSQS) has been launched in Japan to improve surgical safety. This study aimed to determine whether ESSQS-qualified surgeons affect the short- and long-term outcomes of laparoscopic right hemicolectomy. METHODS: A total of 187 colon cancer patients who underwent laparoscopic right hemicolectomy at Kindai University Hospital between January 2016 and December 2020 were enrolled. These patients were divided into two groups based on surgeries performed by ESSQS-qualified surgeons (QS group) and non-ESSQS-qualified surgeons (NQS group). The short- and long-term outcomes were compared between the two groups before and after propensity score matching (PSM). RESULTS: After PSM, 43 patients from each group were included in the matched cohort. In the short-term outcomes, the total operative time was significantly longer in the NQS group than in the QS group (229 vs. 174 min, p < 0.0001). However, there were no significant differences in the two groups regarding blood loss (0 vs. 0 ml, p = 0.7126), conversion (0.0% vs. 7.0%, p = 0.0779), Clavien-Dindo ≥ 2 complications (9.3% vs. 7.0%, p = 0.6933), mortality (2.3% vs. 0.0%, p = 0.3145), and postoperative hospital stay (9 vs. 9 days, p = 0.5357). In the long-term outcomes, there were no significant differences between the two groups in the 3-year overall survival (86.6% vs. 83.0%, p = 0.8361) and recurrence-free survival (61.7% vs. 72.0%, p = 0.3394). CONCLUSION: Laparoscopic right hemicolectomy performed by ESSQS-qualified surgeons contributed to shorter operative time. Under the supervision of ESSQS-qualified surgeons, almost equivalent safety and oncological outcomes are expected even in surgeries performed by non-ESSQS-qualified surgeons.

Japanese multicenter prospective study investigating laparoscopic surgery for locally advanced rectal cancer with evaluation of CRM and TME quality (PRODUCT trial).

Aim: In Japan, we have not been able to validate the results of laparoscopic surgery for locally advanced rectal cancer using the universal index "circumferential resection margin (CRM)." Previously, we established a semi-opened circular specimen processing method and validated its feasibility. In the PRODUCT trial, we aimed to assess CRM in patients with locally advanced rectal cancer who underwent laparoscopic rectal resection. Methods: This was a multicenter, prospective, observational study. Eligible patients had histologically confirmed rectal adenocarcinoma located at or below 12 cm above the anal verge with clinical stage II or III and were scheduled for laparoscopic or robotic surgery. The primary endpoint was pathological CRM. CRM ≤1 mm was defined as positive. Results: A total of 303 patients operated on between August 2018 and January 2020 were included in the primary analysis. The number of patients with clinical stage II and III was 139 and 164, respectively. Upfront surgery was performed for 213 patients and neoadjuvant therapy for 90 patients. The median CRM was 4.0 mm (IQR, 2.1-8.0 mm), and CRM was positive in 26 cases (8.6%). Univariate and multivariate analyses demonstrated that a predicted CRM from the mesorectal fascia of ≤1 mm on MRI was the significant factor for positive CRM (P = .0012 and P = .0045, respectively). Conclusion: This study showed the quality of laparoscopic rectal resection based on the CRM in Japan. Preoperative MRI is recommended for locally advanced rectal cancer to prevent CRM positivity.

A Narrative Review of the Usefulness of Indocyanine Green Fluorescence Angiography for Perfusion Assessment in Colorectal Surgery.

Anastomotic leakage is one of the most dreaded complications of colorectal surgery and is strongly associated with tissue perfusion. Indocyanine green fluorescence angiography (ICG-FA) using indocyanine green and near-infrared systems is an innovative technique that allows the visualization of anastomotic perfusion. Based on this information on tissue perfusion status, surgeons will be able to clearly identify colorectal segments with good blood flow for safer colorectal anastomosis. The results of several clinical trials indicate that ICG-FA may reduce the risk of AL in colorectal resection; however, the level of evidence is not high, as several other studies have failed to demonstrate a reduction in the risk of AL. Several large-scale RCTs are currently underway, and their results will determine whether ICG-FA is, indeed, useful. The major limitation of the current ICG-FA evaluation method, however, is that it is subjective and based on visual assessment by the surgeon. To complement this, the utility of objective evaluation methods for fluorescence using quantitative parameters is being investigated. Promising results have been reported from several clinical trials, but all trials are preliminary owing to their small sample size and lack of standardized protocols for quantitative evaluation. Therefore, appropriately standardized, high-quality, large-scale studies are warranted.

A Highly Conductive n-Type Coordination Complex with Thieno[3,2-b]thiophene Units: Facile Synthesis, Orientation, and Thermoelectric Properties.

An organometallic nickel complex containing thieno[3,2-b]thiophene units was designed and synthesized. Composite films of the resulting nickel complex and polyvinylidene difluoride, which can be fabricated via a simple solution process under atmospheric conditions, exhibit remarkably high n-type conductivity (>200 S cm-1). Moreover, the thermoelectric power factor of the n-type composite film was proven to be air stable. A grazing-incidence wide-angle X-ray diffraction analysis indicated a significant impact of introducing the thieno[3,2-b]thiophene core into the backbone of the nickel complex on the orientation within the composite films.

Recruitment of Peroxin 14 to lipid droplets affects lipid storage in Drosophila.

Both peroxisomes and lipid droplets regulate cellular lipid homeostasis. Direct inter-organellar contacts as well as novel roles for proteins associated with peroxisome or lipid droplets occur when cells are induced to liberate fatty acids from lipid droplets. We have shown a non-canonical role for a subset of peroxisome-assembly [Peroxin (Pex)] proteins in this process in Drosophila. Transmembrane proteins Pex3, Pex13 and Pex14 were observed to surround newly formed lipid droplets. Trafficking of Pex14 to lipid droplets was enhanced by loss of Pex19, which directs insertion of transmembrane proteins like Pex14 into the peroxisome bilayer membrane. Accumulation of Pex14 around lipid droplets did not induce changes to peroxisome size or number, and co-recruitment of the remaining Peroxins was not needed to assemble peroxisomes observed. Increasing the relative level of Pex14 surrounding lipid droplets affected the recruitment of Hsl lipase. Fat body-specific reduction of these lipid droplet-associated Peroxins caused a unique effect on larval fat body development and affected their survival on lipid-enriched or minimal diets. This revealed a heretofore unknown function for a subset of Pex proteins in regulating lipid storage. This article has an associated First Person interview with Kazuki Ueda, joint first author of the paper.

Effectiveness of negative pressure wound therapy with instillation and dwelling after stoma closure: a retrospective and propensity score matching analysis.

The use of temporary diverting stoma has become more common in low colorectal anastomosis to reduce anastomotic complications. Surgical site infection (SSI) at the stoma closure site has been one of the most frequent postoperative complications. The aim of this study was to compare the short-term outcomes between conventional primary suture closure and negative pressure wound therapy with instillation and dwelling (NPWTi-d) therapy following purse-string suturing, using propensity score matching analysis. We retrospectively evaluated the medical records of 107 patients who underwent stoma closure between January 2016 and October 2020. The primary outcome was the proportion of SSI. The secondary outcome was the day of postoperative length of stay. Propensity score matching with one-to-one match was performed for reducing treatment selection bias. Of a total of 107 patients, 67 patients had been treated with conventional primary closure and 40 with NPWTi-d therapy. The propensity score matching derived 37 pairs. The respective SSI proportions were 0% and 16.2% in the groups with NPWTi-d and primary closure (P = 0.025). The respective median days of postoperative hospital stay were 9.0 and 10.0 in the groups with NPWTi-d and primary closure (P = 0.453). NPWTi-d therapy with purse-string suturing was effective in reducing SSI after stoma closure.

Laparoscopic complete mesocolic excision with central vascular ligation for splenic flexure colon cancer: short- and long-term outcomes.

BACKGROUND: Complete mesocolic excision (CME) with central vascular ligation (CVL) for colon cancer is an essential procedure for improved oncologic outcomes after surgery. Laparoscopic surgery for splenic flexure colon cancer was recently adopted due to a greater understanding of surgical anatomy and improvements in surgical techniques and innovative surgical devices. METHODS: We retrospectively analyzed the data of patients with splenic flexure colon cancer who underwent laparoscopic CME with CVL at our institution between January 2005 and December 2017. RESULTS: Forty-five patients (4.8%) were enrolled in this study. Laparoscopic CME with CVL was successfully performed in all patients. The median operative time was 178 min, and the median estimated blood loss was 20 g. Perioperative complications developed in 6 patients (13.3%). The median postoperative hospital stay was 9 days. According to the pathological report, the median number of harvested lymph nodes was 15, and lymph node metastasis developed in 14 patients (31.1%). No metastasis was observed at the root of the middle colic artery or the inferior mesenteric artery. The median follow-up period was 49 months. The cumulative 5-year overall survival and disease-free survival rates were 85.9% and 84.7%, respectively. The cancer-specific survival rate in stage I-III patients was 92.7%. Recurrence was observed in 5 patients (11.1%), including three patients with peritoneal dissemination and two patients with distant metastasis. CONCLUSIONS: Laparoscopic CME with CVL for splenic flexure colon cancer appears to be oncologically safe and feasible based on the short- and long-term outcomes in our study. However, it is careful to introduce this procedure to necessitate the anatomical understandings and surgeon's skill. The appropriate indications must be established with more case registries because our experience is limited.

Oncocytic Adrenocortical Carcinoma With Low 18F-FDG Uptake and the Absence of Glucose Transporter 1 Expression.

Adrenocortical carcinoma (ACC) is a rare tumor, and some histological variants (oncocytic, myxoid, and sarcomatoid ACCs) have been reported in addition to the conventional ACC. Among these subtypes, oncocytic ACC is histologically characterized by the presence of abundant eosinophilic granular cytoplasm in the carcinoma cells owing to the accumulation of mitochondria, which generally yields high 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Herein, we report the case of a 21-year-old woman with oncocytic ACC with low FDG uptake on PET scan. Her circulating levels of androgens were high, and androgen-synthesis enzymes were detected in carcinoma cells. The patient also had hypocholesterolemia. However, glucose transporter 1 (GLUT1) was not detected in the tumor, which was considered to account for the low FDG uptake by the tumor. To the best of our knowledge, this is the first case of low FDG uptake by oncocytic ACC without GLUT1 expression. Additionally, since hypocholesterolemia was reported in 3 previous reports of androgen-producing tumors, a possible correlation between androgenicity in adrenal tumors and the development of hypocholesterolemia could be postulated; however, further investigations are needed for clarification. This case highlights important information regarding the diversity of ACC and its impact on hypocholesterolemia.

Hybrid method using laparoscopy and Lichtenstein's technique for incarcerated inguinal hernia in a patient with liver cirrhosis and severe varicose veins: A case report.

INTRODUCTION: Cirrhosis is a significant determinant of postoperative morbidity and mortality. Patients with severe liver cirrhosis are substantially contraindicated for surgical treatment of inguinal hernia because of the substantial recurrence rate and high postoperative morbidity and mortality. However, hernia with incarceration and strangulation, which could become life-threatening, should be repaired urgently even for patients with severe liver cirrhosis. No clear surgical guidelines have been established regarding the treatment strategy for inguinal hernia in patients with cirrhosis. PRESENTATION OF CASE: A 62-year-old man with a history of chronic C-type liver cirrhosis (Child-Pugh classification C) and hepatocellular carcinoma was referred to us for surgical treatment of an irreducible right inguinal hernia. An abdominal computed tomography (CT) scan revealed that the small intestine had herniated into the scrotum and severe abdominal wall varicose veins due to liver cirrhosis. We performed a hybrid method that combines examination laparoscopy and Lichtenstein's technique to observe the abdominal cavity and to avoid the risks due to severe varicosis of the inferior epigastric vein. DISCUSSION: There have been some reports of inguinal hernia with cirrhosis and ascites, but no reports of incarcerated inguinal hernia with abdominal wall varicose veins. In the present case, we chose a laparoscopic approach to observe the abdominal cavity to confirm intestinal necrosis. Hybrid surgery using laparoscopy and Lichtenstein's technique for incarcerated inguinal hernia could be performed safely. CONCLUSION: Hybrid surgery using laparoscopy and Lichtenstein's technique may be an effective method for patients with incarcerated inguinal hernia with end-stage cirrhosis and severe abdominal varicosis.

Successful treatment of intractable chylous ascites after laparoscopic low anterior resection using lymphangiography and embolization with lipiodol: A case report.

INTRODUCTION AND IMPORTANCE: Chylous ascites (CA) is an infrequent, intractable complication that may arise after abdominal surgery. Although various attempts at treatment have been adopted, to date, none of them have been consistently effective. We describe the successful treatment of CA using lymphangiography and embolization with lipiodol. CASE PRESENTATION: A 79-year-old woman underwent laparoscopic surgery for rectum cancer at another hospital. She was discharged on postoperative day (POD) 9; however, she had to be treated and hospitalized for CA three times until POD 76. She visited our hospital to undergo treatment for CA on POD 90 because the previous conservative treatment had not improved her condition. The computed tomography (CT) scans revealed ascites effusion. We performed lymphangiography and embolization with lipiodol two times. Repeated CT on POD 134 showed that the ascites had not increased. CLINICAL DISCUSSION: Lymphangiography and embolization with lipiodol effectively resolved chylous leakage that occurred after abdominal surgery. Additionally, we compare the features of two groups of cases of CA: one group in which patients were treated by lymphatic intervention and the second in which patients were treated through surgical procedures. CONCLUSION: We were thus able to demonstrate the clinical effectiveness of lipiodol lymphangiography in treating CA.

Laparoscopic repair of diaphragmatic hernia after radiofrequency ablation for hepatocellular carcinoma: Case report.

INTRODUCTION AND IMPORTANCE: We describe the case of a patients with a diaphragmatic hernia associated with radiofrequency ablation for hepatocellular carcinoma who was treated by laparoscopic repair. CASE PRESENTATION: An 82-years-old man with history of HCC with hepatitis C virus-related liver cirrhosis (Child-Pugh B). The patient was treated RFA to HCC for segment 4, 5, 6, 8. After 16 months from latest RFA for segment 8, the patient was admitted to our hospital because of mild dyspnea. Computed tomography revealed a diaphragmatic herniation of bowel loops into the right thoracic cavity. The patients electively underwent laparoscopic repair of the diaphragmatic hernia. The patient was discharged from hospital without any post-operative complications. CLINICAL DISCUSSION: The only treatment to diaphragmatic hernia is surgery, but liver cirrhosis patients limits this possibility. For the surgical treatment of patients with severe cirrhosis, the operation should be carefully assessed. We believe that a laparoscopic approach should be used for repairing diaphragmatic hernia. In the present case, we considered that a laparoscopic approach was safer and more feasible than open laparotomy. CONCLUSION: Diaphragmatic hernia is a rare late-onset complication associated with RFA for HCC. And patients with HCC often have severe liver dysfunction and cirrhosis. A laparoscopic approach is safe and minimally invasive for sever cirrhosis patients.

The technique for less infectious and earlier healing of stoma closure wound: negative pressure wound therapy with instillation and dwelling followed by primary closure.

BACKGROUND: Temporary stomas have been widely used to avoid the risk of complications such as anastomotic leakage after colorectal resection. Stoma closure is relatively easy; however, postoperative surgical site infection (SSI) may be a problem. Various methods have been used to reduce the incidence of SSI. We aimed to evaluate a new technique for stoma wound closure. METHODS: We enrolled patients who underwent stoma closure at our hospital between September 2019 and May 2020. We selected patients who lived far from our hospital and had difficulty visiting the hospital regularly and who agreed to undergo this surgical technique. We used negative pressure wound therapy with instillation and dwelling (NPWTi-d) and delayed primary closure for these patients. RESULTS: Four patients underwent NPWTi-d and delayed primary closure without the occurrence of SSI. The median postoperative hospital stay was 9 days (range: 7-14 days), and the median number of days to confirmation of epithelialization was 11.5 days (range: 10-16 days). CONCLUSION: The combined use of NPWTi-d and delayed primary closure for the stoma wound was very effective. This method may be a valuable new technique for wound management after stoma closure.

A Rare Case of Adrenal Cysts Associated With Bilateral Incidentalomas and Diffuse Hyperplasia of the Zona Glomerulosa.

Characterization of adrenocortical disorders is challenging because of varying origins, laterality, the presence or absence of hormone production, and unclarity about the benign or malignant nature of the lesion. Histopathological examination in conjunction with immunohistochemistry is generally considered mandatory in this characterization. We report a rare case of bilateral adrenocortical adenomas associated with unilateral adrenal endothelial cysts in a 65-year-old woman whose condition was not diagnosed before surgery. Detailed histological examination of the resected adrenal glands revealed hyperplasia in the zona glomerulosa. Despite hyperplasia, the patient had normal serum aldosterone levels and renin activity without clinical evidence of hypertension. The patient was treated with a sodium-glucose cotransporter protein 2 (SGLT2) inhibitor. This may have stimulated the renin-angiotensin-aldosterone system. To the best of our knowledge, this is the first case in which both relatively large bilateral adrenocortical adenomas and unilateral adrenal endothelial cysts were detected. This case also highlights the complexity and difficulty of preoperative diagnosis. Furthermore, this case reports the first detailed histopathological examination of adrenal lesions with SGLT2 treatment and the possibility of SGLT2 inhibitor treatment resulting in histological hyperplasia in the zona glomerulosa; however, it is difficult to prove a causative relationship between SGLT2 inhibitors and hyperplasia of the zona glomerulosa based on the data of this case. It can be confirmed only under limited conditions; therefore, further studies on adrenal gland histology employing SGLT2 inhibition are warranted.

Visualization of lymphatic flow in laparoscopic colon cancer surgery using indocyanine green fluorescence imaging.

Intraoperative visualization of lymphatic flow could guide surgeons performing laparoscopic colon cancer surgery on the extent of intestinal resection required. The purpose of this study was to investigate indocyanine green fluorescence imaging for intraoperative detection of lymphatic flow and nodes in such patients. All patients undergoing elective laparoscopic surgery for colorectal cancer from October 2016 to July 2017 were included in this study. Indocyanine green was injected submucosally around the tumors via a colonoscope and lymphatic flow assessed with a laparoscopic near-infrared camera system intraoperatively. Lymphatic flow was visualized perioperatively in 43 of 57 patients (75.4%). The rate of visualized lymphatic flow was significantly higher in patients with a lower clinical stage than in those with a higher clinical stage (p = 0.0103). Among the 14 patients in whom lymphatic flow was not visualized, 10 (71.4%) had cStage III or IV cancer. Our results indicate the potential role of intraoperative navigation in colon cancer surgery in early-stage colon cancers. This method allows the surgeon to clearly identify lymphatic flow during surgery and allows the determination and individualization of the lymph node dissection range.

Rosy Beginnings: Studying Peroxisomes in Drosophila.

Research using the fruit fly Drosophila melanogaster has traditionally focused on understanding how mutations affecting gene regulation or function affect processes linked to animal development. Accordingly, flies have become an essential foundation of modern medical research through repeated contributions to our fundamental understanding of how their homologs of human genes function. Peroxisomes are organelles that metabolize lipids and reactive oxygen species like peroxides. However, despite clear linkage of mutations in human genes affecting peroxisomes to developmental defects, for many years fly models were conspicuously absent from the study of peroxisomes. Now, the few early studies linking the Rosy eye color phenotype to peroxisomes in flies have been joined by a growing body of research establishing novel roles for peroxisomes during the development or function of specific tissues or cell types. Similarly, unique properties of cultured fly Schneider 2 cells have advanced our understanding of how peroxisomes move on the cytoskeleton. Here, we profile how those past and more recent Drosophila studies started to link specific effects of peroxisome dysfunction to organ development and highlight the utility of flies as a model for human peroxisomal diseases. We also identify key differences in the function and proliferation of fly peroxisomes compared to yeast or mammals. Finally, we discuss the future of the fly model system for peroxisome research including new techniques that should support identification of additional tissue specific regulation of and roles for peroxisomes.

Aortic Mural Thrombus Associated with Congenital Protein C Deficiency in an Elderly Patient.

Thrombophilia increases the risk of venous thrombosis, but is rarely responsible for aortic thrombosis. Aortic mural thrombus (AMT) may be associated with a protein C deficiency. However, it is necessary to determine whether the protein C deficiency is congenital/hereditary or secondary/acquired (consumption of protein C during the process of thrombus formation). This study describes a 77-year-old Japanese woman with incidentally diagnosed AMT, who had a protein C deficiency (activity 54%, antigen 42%). Sequencing of the protein C gene revealed a heterozygous mutation of c.1268delG, p.Gly423Valfs＊82 in exon 9, indicating a congenital protein C deficiency. These findings indicate that very late onset AMT can occur in an adult with congenital protein C deficiency.