Stereotactic navigation using registration based on intra-abdominal landmarks in robotic-assisted lateral pelvic lymph node dissection.

BACKGROUND: We carried out robot-assisted lateral pelvic lymph node dissection (LPLND) for rectal cancer with a stereotactic navigation system. The purpose of this study was to evaluate the accuracy and feasibility of the system. METHODS: We constructed a navigation system based on the Polaris Spectra optical tracking device (Northern Digital Inc., Canada) and the open-source software 3D Slicer (version 3.8.1; http://www.slicer.org ). We used the landmark-based registration method for patient-to-image registration. Body surface landmarks and intra-abdominal landmarks were used. We evaluated the time required for registration and target registration error (TRE; the distance between corresponding points after registration) for the root of the superior gluteal artery the root of the obturator or superior vesical artery, and the obturator foramen during minimally invasive LPLND for rectal cancer. Five patients who had LPLND for rectal cancer at the University of Tokyo Hospital between September 2020 and May 2021 were enrolled. RESULTS: The mean time required for registration was 49 s with the body surface landmarks and 88 s with the intra-abdominal landmarks. The mean TRE improved markedly when the registration was performed using intra-abdominal landmarks. The mean TRE of the root of the superior gluteal artery, the root of the obturator or superior vesical artery, and the obturator foramen were 55.8 mm, 53.4 mm, and 55.2 mm with the body surface landmarks and 11.8 mm, 10.0 mm, and 12.6 mm with the intra-abdominal landmarks, respectively. There were no adverse events related to the registration process. CONCLUSIONS: When stereotactic navigation systems are used for minimally invasive LPLND, the use of intra-abdominal landmarks for registration is feasible and may allow simpler and more accurate navigation than the use of body surface landmarks.

Classification of the colonic splenic flexure based on three-dimensional CT analysis.

BACKGROUND: Mobilization of the splenic flexure can be a challenging surgical step in colorectal surgery. This study aimed to classify the splenic flexure based on the three-dimensional (3D) coordinates of the splenic hilum and left renal hilum. This classification was used to compare splenic flexure mobilization during colorectal resection. METHODS: CT images of patients with colorectal cancer treated between April 2018 and December 2019 were analysed retrospectively. 3D mutual positioning of the splenic flexure from the ligament of Treitz to the splenic hilum or the left renal hilum was used to classify patients into three groups using cluster analysis. The difference in the procedure time between groups was also analysed in a subset of patients undergoing laparoscopic colectomy with complete splenic flexure mobilization. RESULTS: Of 515 patients reviewed, 319 with colorectal cancers were included in the study and categorized based on the 3D coordinates of the splenic hilum and left renal hilum as caudal (100 patients), cranial (118) and lateral (101) positions. Male sex (P < 0.001), older age (P = 0.004) and increased bodyweight (P = 0.043) were independent characteristics of the lateral group in multiple logistic regression analysis. Thirty-four patients underwent complete splenic flexure mobilization during the study period; this took significantly longer (mean 78.7 min) in the lateral group than in the caudal and cranial groups (41.8 and 43.2 min respectively; P = 0.006). CONCLUSION: Locating the splenic flexure using 3D coordinates could be helpful in predicting a longer duration for mobilization of the splenic flexure.

Utility of computed tomography and 18 F-fluorodeoxyglucose with positron emission tomography/computed tomography for distinguishing appendiceal mucocele caused by mucinous adenocarcinoma from other pathologies.

AIM: Differentiating appendiceal mucocele with mucinous adenocarcinoma from other pathologies before surgery is difficult. The objective of this study was to evaluate the utility of CT and 18 F-fluorodeoxyglucose (FDG) with positron emission tomography (PET)/CT for differentiating mucinous adenocarcinoma of appendiceal mucocele from other pathologies. METHOD: The study included 25 patients who underwent surgery for clinically diagnosed appendiceal mucoceles detected on CT at the University of Tokyo Hospital. Among these patients, 19 underwent FDG-PET/CT preoperatively. We compared features of the CT imaging findings and maximum standard uptake values (SUVmax ) detected by FDG-PET/CT between mucocele with mucinous adenocarcinoma and other pathologies. RESULTS: A total of 13 men (52%) and 12 women (48%) were included in this study, with a median age of 65 years (range 34-83). There were six patients (24%) with pathologically confirmed mucinous adenocarcinoma, 15 patients (60%) with appendiceal mucinous neoplasm and four patients (16%) with simple mucocele caused by chronic inflammation. On the CT findings, wall irregularity was the only significant feature for the two groups in this study (83.3% vs 0.0%, P < 0.01). There was a significant difference in the SUVmax levels on PET/CT between the two groups (100.0% vs 20.0%, P < 0.01). CONCLUSION: Distinguishing between mucocele with mucinous adenocarcinoma and other pathologies using imaging modalities is challenging. Our results suggest that wall irregularity on CT and elevated SUVmax on PET/CT are useful factors that can be employed for such discrimination.

Potential Usefulness of Three-dimensional Navigation Tools for the Resection of Intra-abdominal Recurrence of Colorectal Cancer.

PURPOSE: Complete resection of intra-abdominal recurrence of colorectal cancer is difficult because of complex anatomical changes following primary surgery and indefinite cancer demarcation. Here, we demonstrate the effect of surgery using three-dimensional (3D) printed model and 3D virtual images on the achievement of complete resection. METHODS: We enrolled 11 cases who had undergone combined resection of adjacent organs for colorectal cancer recurrence, including localized peritoneal dissemination of colon cancer and local recurrence of rectal cancer, between January 2016 and July 2018. We created 3D virtual images of nine cases and 3D models of two cases and used them for intraoperative navigation. RESULTS: Simulation and navigation using 3D technologies potentially helped the surgeons to comprehend the complex anatomy and perform challenging surgeries. Macroscopic negative margins were achieved in all cases, including R0 resection in 8 of the 11 cases. CONCLUSION: 3D navigation tools are potentially useful to complete the resection of intra-abdominal recurrence of colorectal cancer.

Effects of preceding endoscopic treatment on laparoscopic surgery for early rectal cancer.

AIM: Endoscopic treatment for rectal cancer, such as endoscopic mucosal resection and endoscopic submucosal dissection, causes inflammation, oedema and fibrosis in the surrounding tissue. However, little is known about the effect of these endoscopic therapies on salvage laparoscopic rectal surgery. The objective of this retrospective cohort study was to analyse the effect of preceding endoscopic treatment on the outcomes of laparoscopic surgery for rectal cancer. METHOD: We analysed 53 patients who underwent laparoscopic surgery for rectal cancer with clinical Tis or T1 at our department between May 2011 and June 2019. Data from 30 patients who underwent laparoscopic surgery after preceding endoscopic treatment (Group E + S) were compared with those of 23 patients who underwent laparoscopic surgery alone (Group S). RESULTS: There was no significant difference between the groups with respect to preoperative details. The mean operative time tended to be longer in Group E + S, and the volume of intra-operative blood loss was greater in Group E + S than in Group S (median 63 ml vs 10 ml, P = 0.049). There were no significant differences between the groups in other surgical parameters or oncological outcomes. CONCLUSION: Laparoscopic surgery after endoscopic treatment for rectal cancer may be difficult due to an increased risk of intra-operative bleeding. Long-term prognosis after surgery was not affected by preceding endoscopic treatment in rectal cancer.

Incidence of and risk factors for lymphocele formation after lateral pelvic lymph node dissection for rectal cancer: a retrospective study.

AIM: Pelvic lymphocele is a common complication that develops after pelvic lymph node dissection. The incidence of pelvic lymphocele formation has been reported to be 10.5-51% after gynaecological or urological procedures. However, no evidence has been reported thus far with regard to the development of pelvic lymphocele following lateral pelvic lymph node dissection (LPND) for low rectal cancer. The aim of this study was to investigate the incidence of and risk factors for lymphocele formation after LPND for low rectal cancer and to examine its clinical management. METHOD: We retrospectively analysed the incidence of and risk factors for pelvic lymphocele formation after LPND for rectal cancer in our hospital between January 2012 and December 2017. We also compared the size of the lymphocele between asymptomatic and symptomatic patients by using CT volumetry and examined its clinical management. RESULTS: A total of 30 out of 98 patients (30.8%) developed pelvic lymphocele after rectal LPND. The number of resected nodes was significantly higher in patients with a pelvic lymphocele (P < 0.01). The median volume was significantly higher in patients with symptomatic pelvic lymphocele (P = 0.011). Among the nine symptomatic patients, two underwent CT-guided drainage, one underwent transurethral ureteral stent placement and one underwent laparoscopic marsupialization. CONCLUSION: It is essential to keep in mind the possibility of pelvic lymphocele formation during follow-up of patients who undergo LPND, and to consider an appropriate treatment when these patients are symptomatic.

Vascular anatomy of the splenic flexure, focusing on the accessory middle colic artery and vein.

AIM: Recently, the accessory middle colic artery (AMCA) has been recognized as the vessel that supplies blood to the splenic flexure. However, the positional relationship between the AMCA and inferior mesenteric vein (IMV) has not been evaluated. Herein, we aimed to evaluate the anatomy of the AMCA and the splenic flexure vein (SFV). METHOD: Two hundred and five patients with colorectal cancer who underwent enhanced CT preoperatively were enrolled in the present study. The locations of the AMCA and IMV were evaluated, focusing on the positional relationship between the vessels and pancreas - below the pancreas or to the dorsal side of the pancreas. RESULTS: The AMCA was observed in 74 (36.1%) patients whereas the SFV was found in 177 (86.3%) patients. The left colic artery (LCA) was the major artery accompanying the SFV in 87 (42.4%) of patients. The AMCA accompanied the SFV in 65 (32.7%) patients. In 15 (7.8%) patients, no artery accompanied the SFV. The origin of the AMCA was located on the dorsal side of the pancreas in 15 (20.3%) of these 74 patients. Similarly, the destination of the IMV was located on the dorsal side of the pancreas in 65 (31.7%) of patients. CONCLUSION: The SFV was observed in most patients, and the LCA or AMCA was the common accompanying artery. In some patients these vessels were located on the dorsal side of the pancreas and not below it. Preoperative evaluation of this anatomy may be beneficial for lymph node dissection during left-sided hemicolectomy.

Meta-analysis of the association of extraintestinal manifestations with the development of pouchitis in patients with ulcerative colitis.

Background: The presence of extraintestinal manifestations may be associated with the development of pouchitis in patients with ulcerative colitis after ileal pouch-anal anastomosis. The aim of this study was to assess this correlation. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Library. Studies published in English up to 22 May 2017 investigating the association between extraintestinal manifestations and development of pouchitis in adults with ulcerative colitis were included. Case reports were excluded. The association of extraintestinal manifestations with the development of overall and chronic pouchitis was investigated using a random-effects model. Results: Of 1010 citations identified, 22 observational studies comprising 5128 patients were selected for analysis. The presence of extraintestinal manifestations was significantly associated with both chronic pouchitis (odds ratio 2·28, 95 per cent c.i. 1·57 to 3·32; P = 0·001) and overall pouchitis (odds ratio 1·96, 1·49 to 2·57; P < 0·001). Conclusion: The presence of extraintestinal manifestations is associated with development of pouchitis after ileal pouch-anal anastomosis.

Obstruction is associated with perineural invasion in T3/T4 colon cancer.

AIM: Perineural invasion (PNI) is a risk factor for recurrence and metastasis and consequently leads to decreased survival in patients with various malignancies. Recent studies showed that stent placement in obstructive colon cancer increases the frequency of PNI. We hypothesized that mechanical stress including obstruction itself may be associated with PNI. METHOD: We retrospectively reviewed 496 patients with pathological T3 or T4 colon cancer who did not receive preoperative treatment. Data were collected from medical charts and pathological findings. The relationships between PNI and other clinicopathological factors were analysed using univariate and multivariate analyses. RESULTS: PNI was observed in 239 (48%) patients. Obstruction was markedly more frequent in PNI-positive cancer (39%) than in PNI-negative cancer (24%, P = 0.0003). Multivariate analyses identified obstruction as one of the significant factors associated with PNI (OR 1.68, P = 0.028). Moreover, in 414 patients without distant metastasis who underwent complete resection, PNI was an independent factor associated with poor recurrence-free survival (hazard ratio 2.35, P = 0.003). The coexistence of PNI and obstruction resulted in greater decreases in recurrence-free survival than PNI-negative and/or non-obstructive cases. CONCLUSION: Our results suggest that obstruction is associated with PNI and consequently contributes to an increased postoperative recurrence in colon cancer.

What is the origin of macroscopic friction?

What is the origin of molecular friction, and how can macroscopic friction be explained in terms of molecular friction? To elucidate the origins of molecular and macroscopic friction, we conducted density functional theory calculations and double-direct shear tests at normal stresses ranging from 5 to 60 MPa for mica surfaces. Frictional forces between mica surfaces were theoretically predicted to oscillate periodically every 30° of sliding direction, in agreement with previous experimental findings. This result affirms that the potential energy roughness of mica under sliding is the origin of molecular friction, which depends on the normal stress and sliding direction. The discovered mechanism of molecular friction can quantitatively explain experimentally observed macroscopic friction of mica when the presence of wear particles is taken into consideration.

Administration of Thrombomodulin (CD141) Could Improve Cardiac Allograft Survival in Mice.

Thrombomodulin (TM) is a promising natural anti-coagulant therapeutic protein that is effective in the treatment of disseminated intravascular coagulation. However, the mechanisms by which TM on micro-vessels enable the regulation of intimal hyperplasia remain elusive. We investigated the graft-protective effects of TM in a fully major histocompatibility complex-mismatched murine cardiac allograft transplantation model. CBA recipients transplanted with a C57BL/6 heart received intraperitoneal administration of 0.2, 2.0, and 20.0 µg/day of TM for 8 days. Histological staining was conducted to assess the degree of inflammation and infiltration in the transplanted cardiac grafts. Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST] was 7 days). CBA recipients exposed to the above dosages had significantly prolonged allograft survival (MSTs were 16, 21, and 37.5 days, respectively). Histologic assessments from TM-exposed recipients 2 weeks after grafting showed that the myocardium and vessel structure in their allografts were clearly preserved, and that the infiltration of inflammatory cells around coronary arteries was suppressed. TM can induce the prolongation of fully major histocompatibility complex-mismatched cardiac allograft by exerting graft protective effects within the myocardium and coronary arteries.

More Hippocampal Weight and Cells in Cardiac Allograft Transplanted Mice.

The hippocampus is a brain structure that plays a fundamental role in memory and learning. Many animal studies have demonstrated that the structure of the hippocampus has evolved through exercise and play. However, little is known on the relationship between the brain and immunological reaction. In this study, we investigated the correlation between the weight of the hippocampus and transplant immunology in a murine heart transplant model. Fully vascularized heterotopic hearts from CBA (H2k, allogeneic group) or C57BL/6 (H2b, syngeneic group) donors were transplanted into C57BL/6 recipients by using microsurgical techniques. The weights of the whole brain and hippocampus from syngeneic and allogeneic groups were recorded 1, 2, and 4 weeks after grafting, and histologic assessments were performed. The syngeneic group maintained beating cardiac grafts for over 30 days, but the allogeneic group rejected CBA cardiac allografts acutely within 8 days. The average weight of whole brain from syngeneic and allogeneic group 1, 2, and 4 weeks had no significant differences. However, the average weight of hippocampus at 2 and 4 weeks was considerably increased in the allogeneic group compared with the syngeneic group. Histologic assessments with hematoxylin-eosin and Kluver-Barrera staining of hippocampus from allogeneic group 1 week after grafting demonstrated a greater number of granule and pyramidal cells in the hippocampus. Alloimmune responses in our model increase the weight of hippocampus.

Evaluation of the vascular anatomy of the left-sided colon focused on the accessory middle colic artery: a single-centre study of 734 patients.

AIM: Surgery for colorectal cancer located in the splenic flexure is difficult to perform because of the complex anatomy. Recently, in addition to the middle colic artery and left colic artery (LCA), the accessory middle colic artery (AMCA) has been recognized as a feeding artery for the left-sided colon. This study aimed to evaluate the vascular anatomy of the splenic flexure focusing on the AMCA in a large number of patients. METHOD: A total of 734 patients who underwent CT before surgery for colorectal cancer were enrolled. We retrospectively evaluated the vascular anatomy using both two- and three-dimensional CT angiography. RESULTS: The AMCA existed in 36.4% of the cases (n = 267). In many cases, it originated from the superior mesenteric artery (n = 228, 85.4%). The AMCA had a common trunk with the transverse pancreatic artery in 54 patients (20.2%). The frequency of the presence of the AMCA was associated with the branching pattern of the LCA, and was more frequent when the LCA was absent (P < 0.001). CONCLUSION: The presence of the AMCA is not rare and the AMCA has some branching patterns; therefore, recognizing it preoperatively and intra-operatively is important, being especially careful when the LCA is absent.

Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study.

AIM: Clinical guidelines recommend adjuvant chemotherapy for high-risk patients with Stage II-III colorectal cancer. However, chemotherapeutic administration rates differ significantly between hospitals. We assessed the prognostic benefit of adjuvant chemotherapy in patients with Stage IIb/c colorectal cancer, and the prognostic impact of interhospital variations in the administration of adjuvant chemotherapy for Stage II-III colorectal cancer. METHOD: We conducted a multicentre, retrospective study of 17 757 patients with Stage II-III colorectal cancer treated between 1997 and 2008 in 23 hospitals in Japan. Hospitals were classified as high-rate (rate > 42.8%) or low-rate (rate ≤ 42.8%), chemotherapy prescribing clinics. RESULTS: The 5-year overall survival (OS) of patients with Stage II-III colorectal cancer receiving adjuvant chemotherapy was significantly higher than for those not receiving adjuvant chemotherapy (85.7% vs 79.2%, P < 0.01 and 79.9% vs 72.5%, P < 0.01, respectively). For patients with Stage II disease, adjuvant chemotherapy was an independent factor for longer OS (P < 0.01, hazard ratio = 0.71). Both adjuvant chemotherapy and high-rate hospital independently improved OS for patients with Stage III colorectal cancer (both P < 0.01; hazard ratio = 0.68 and 0.87, respectively). CONCLUSION: Significant prognostic benefit was found for patients with Stage IIb/c colorectal cancer who received adjuvant chemotherapy, with patients who were treated in hospitals with high adjuvant chemotherapy rates demonstrating better prognoses.

Diagnostic value of FDG-PET/CT for lateral pelvic lymph node metastasis in rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: The aim of this study was to elucidate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) for lateral pelvic lymph node (LPN) metastasis in rectal cancer treated with preoperative chemoradiotherapy (CRT). METHODS: Eighteen rectal cancer patients with enlarged (≥ 8 mm) LPNs were treated with CRT followed by total mesorectal excision with LPN dissection during 2012-2015. After CRT, LPN maximum standard uptake values (SUVmax) were measured using PET/CT and long diameters of LPNs were measured using CT or magnetic resonance imaging (MRI). LPN size and SUVmax were compared with pathological status in the resected specimen. Radiologically identified nodes were matched with surgically resected nodes by separate examination of 4 lymph nodal regions: internal iliac, obturator, external iliac and common iliac lymph nodes. RESULTS: In total, 34 LPNs were located by CT or MRI. Metastatic LPNs were significantly larger than non-metastatic LPNs (size, mean ± standard deviation: 13.0 ± 8.3 vs. 4.9 ± 3.5 mm, p < 0.01). SUVmax was determinable for 28 of the LPNs, among which metastatic LPNs were found to have significantly higher SUVmax than non-metastatic LPNs (mean ± standard deviation: 2.2 ± 1.3 vs. 1.2 ± 0.3, p < 0.01). Receiver operating characteristic analysis suggested optimal cutoff values of size = 12 mm which had an accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 82.1, 70.6, 100, 100, and 68.8%, respectively. An SUVmax = 1.6 had an accuracy, sensitivity, specificity, PPV, and NPV of 85.7, 76.5, 100, 100, and 73.3%, respectively. When LPNs that were ≥ 12 mm in size and/or had an SUV ≥ 1.6, the accuracy, sensitivity, specificity, PPV, and NPV were 92.9, 88.2, 100, 100, and 84.6%, respectively. CONCLUSIONS: After CRT, PET/CT alone or in combination with CT and MRI can predict the presence of metastatic LPN with a high degree of accuracy. PET/CT may be useful in selecting patients with rectal cancer who would benefit from LPN dissection in addition to TME. These results need to be confirmed by larger studies.

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients.