Impact of the lateral skeletal stability following bilateral sagittal split ramus osteotomy for mandibular asymmetry.

This study evaluated the stability of bilateral sagittal split ramus osteotomy (BSSRO) associated with positional plagiocephaly and temporal and masseter muscles using posteroanterior cephalogram analysis and three-dimensional computed tomography (3D-CT). This retrospective cohort study included 31 patients who underwent BSSRO for mandibular asymmetry. The cranial vault asymmetry index (CVAI) and the cephalic index were used as indicators of positional plagiocephaly. The distance from the vertical reference line to the menton (Me) was measured on posteroanterior cephalograms immediately and 1 year after surgery, and postoperative stability was assessed. Temporal and masseter muscles were constructed from 3D-CT data and their volumes were measured. Simple regression analysis showed a significant correlation between postoperative changes in the vertical reference line to the Me and the CVAI (R = 0.56, p = 0.001), the amount of surgical movement in the vertical reference line to the Me (R = 0.41, p = 0.023), and the variable temporal muscle volume (R = 0.27, p = 0.028). There was no significant correlation between postoperative changes in the vertical reference line to the Me and the cephalic index (R = 0.093, p = 0.62) and variable masseter muscle volume (R = 0.16, p = 0.38). According to multivariate analysis, CVAI (p = 0.003) and amount of surgical movement in the vertical reference line to the Me (p = 0.014) were significant predictors of postoperative change in the vertical reference line to the Me. Positional plagiocephaly and amount of surgical movement influence lateral skeletal stability following BSSRO for mandibular asymmetry.

Spontaneous regression of malignant lymphoma of the maxillary gingiva following biopsy.

A case of spontaneous regression of malignant lymphoma of the maxillary gingiva following a biopsy is reported. An 84-year-old man was referred to the hospital with chief complaints of swelling of the anterior maxillary gingiva. A non-tender swelling with an ulcer was observed. There was no abnormal bone resorption in the anterior maxillary region and no swelling of the cervical lymph nodes. A biopsy was performed, and the patient was diagnosed with diffuse large B-cell lymphoma. The lesion regressed spontaneously 3 weeks after the initial biopsy. Two years have passed since the spontaneous regression and no recurrence has been observed. If malignant lymphoma regresses on biopsy, observation is considered to be sufficient.

Evaluation of vascular anatomy for colon cancer located in the splenic flexure using the preoperative three-dimensional computed tomography angiography with colonography.

PURPOSE: The aim of this study is to reveal the vascular branching variation in SFC (splenic flexure cancer) patients using the preoperative three-dimensional computed tomography angiography with colonography (3D-CTAC). METHODS: We retrospectively analyzed patients with SFC who underwent preoperative 3D-CTAC between January 2014 and December 2019. RESULTS: Among 1256 colorectal cancer (CRC) patients, 96 (7.6%) manifested SFC. The arterial branching from the superior mesenteric artery (SMA) was classified into five patterns, as follows: (type 1A) the left branch of middle colic artery (LMCA) diverged from middle colic artery (MCA) (N = 47, 49.0%); (2A) the LMCA diverged from the MCA and the accessory middle colic artery (AMCA) (N = 26, 27.1%); (3A) the LMCA independently diverged from the SMA (N = 16, 16.7%); (4A) the LMCA independently diverged from the SMA and AMCA (N = 3, 3.1%); (5A) only the AMCA and the LMCA was absent (N = 4, 4.1%). Venous drainage was classified into four patterns, as follows: (type 1V) the SFV flows into the inferior mesenteric vein (IMV) then back to the splenic vein (N = 50, 52.1%); (2V) the SFV flows into the IMV then back to the superior mesenteric vein (SMV) (N = 19, 19.8%); (type 3V) the SFV independently flows into the splenic vein (N = 3, 3.1%); (type 4V) the SFV is absent (N = 24, 25.0%). CONCLUSION: 3D-CTAC could reveal accurate preoperative tumor localization and vascular branching. These classifications should be helpful in performing accurate complete mesocolic excision and central vessel ligation for SFC.

Combined laparoscopic and transperineal endoscopic total pelvic exenteration for local recurrence of rectal cancer.

BACKGROUND: Transanal minimally invasive surgery is a combination of single-port surgery and transanal surgery and was initially developed as a treatment for rectal tumors. Recently, this approach has also been used for more advanced or extended pelvic surgery. METHODS: We present a surgical video of combined laparoscopic and transperineal endoscopic total pelvic exenteration performed in a male patient with recurrent rectal cancer and discuss the pros and cons of this approach. RESULTS: The operating time was 775 min and the operative blood loss was 485 ml. The pathology was recurrent adenocarcinoma invading the prostate and urethra with negative surgical margins. The postoperative course was uneventful except for a urinary tract infection that was treated with antibiotics. CONCLUSIONS: The transanal/perineal endoscopic approach may have some benefits for extended pelvic surgery for recurrent rectal cancer.

Revisiting the treatment strategy for rectal cancer through the pattern of local recurrence.

BACKGROUND: Local recurrence after rectal cancer surgery is categorized as lymphatic spread (pelvic sidewall node (PSN)) and other types. This study aimed to investigate the risk factors associated with different patterns of local recurrence and to optimize the treatment strategy after rectal cancer surgery. METHODS: Patients with cStage I-III rectal cancer who underwent surgery at our institute were included in this study. Local recurrence was categorized as follows: (1) PSN recurrence and (2) "other" types of local recurrence. The risk factors associated with each type of recurrence (metastasis) were investigated. RESULTS: A total of 212 patients with mid/low rectal cancer were included in this study (cStage I: 66; cStage II/III: 146). Additional treatment was employed in selected patients with high-risk features (n = 45; pelvic sidewall dissection: 18; preoperative chemo (radio)therapy: 37). Potential lateral node metastasis was significantly associated with PSN enlargement on imaging findings (no/yes, odds ratio (OR): 9.1; p = 0.007). The "other" local recurrence type was significantly associated with 3 different factors as follows: clinical circumferential resection margin (no/yes; OR: 18.0; p = 0.001), tumor histology (well and moderately/poorly differentiated, OR: 17.3; p = 0.008), and tumor diameter (p = 0.018). Among 146 cStage II/III patients, 66 (45.2%) who did not have any of the abovementioned 4 risk factors experienced no local recurrence even when no additional treatment was employed. CONCLUSIONS: Risk factors may differ for different types of postoperative local recurrence patterns in rectal cancer. Recognizing these risk factors based on pretreatment findings can allow the optimization of treatment strategies for rectal cancer.

Necrosis-induced TLR3 Activation Promotes TLR2 Expression in Gingival Cells.

Damage-associated molecular patterns (DAMPs), endogenous molecules released from injured or dying cells, evoke sterile inflammation that is not induced by microbial pathogens. Periodontal diseases are infectious diseases caused by oral microorganisms; however, in some circumstances, DAMPs might initiate inflammatory responses before host cells recognize pathogen-associated molecular patterns. Here, we showed that the necrotic cell supernatant (NCS) functioned as an endogenous danger signal when released from necrotic epithelial cells exposed to repeat freeze thawing. The NCS contained RNA and stimulated the production of inflammatory cytokines interleukin 6 (IL-6) and IL-8 from gingival epithelial cells and gingival fibroblasts. Targeted knockdown of Toll-like receptor 3 (TLR3) in these cells significantly suppressed the ability of the NCS to induce IL-6 and IL-8 production. Epithelial cells and fibroblasts recognized the NCS from heterologous cells. Interestingly, the activation of TLR3, rather than other TLRs, induced TLR2 mRNA expression and proteins in gingival epithelial cells, and pretreatment with the NCS or polyinosinic:polycytidylic acid (Poly(I:C)), a strong TLR3 activator, enhanced inflammatory cytokine production induced by subsequent stimulation with Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide, a TLR2 agonist. Moreover, the NCS reduced the expression of epithelial tight junction molecules zona occludens 1 and occludin and increased the permeability of epithelial tight junctions. These findings suggest that endogenous danger signal molecules such as self-RNA released from necrotic cells are recognized by TLR3 and that a subsequent increase of TLR2 expression in periodontal compartments such as gingival epithelial cells and gingival fibroblasts may enhance the inflammatory response to periodontopathic microbes recognized by TLR2 such as P. gingivalis, which also disrupts epithelial barrier functions. Thus, DAMPs may be involved in the development and prolongation of periodontal disease.

Distribution of involved abdominal lymph nodes is correlated with the distance from the esophagogastric junction to the distal end of the tumor in Siewert type II tumors.

BACKGROUND: The optimal surgical approach for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) has not yet been agreed. Here we investigated whether the distance from the esophagogastric junction (EGJ) to the distal end of the tumor was related to the distribution of involved abdominal lymph nodes in Siewert type II tumors. METHODS: A total of 288 patients with pT2-4 AEG Siewert II, treated by R0 surgical resection at 7 institutions in Japan, were retrospectively investigated. The distribution of involved abdominal nodes was correlated with the distance from the EGJ to the distal end of the tumor. RESULTS: In patients where the distance from the EGJ to the distal end of the tumor was ≤30 mm, the frequency of nodal involvement along the greater curvature or antrum was low (2.2%). In contrast, in patients where the distance was >50 mm, the incidence of this nodal involvement was 20.0%. In patients where the distance was 30-50 mm incidence was intermediate (8.0%). Multivariate analyses showed that the distance from the EGJ to the distal end of the tumor was significantly related to lymph node involvement along the greater curvature or antrum (odds ratio 3.7, 95% confidence interval 1.3-11, p = 0.006). CONCLUSIONS: When the distance from the EGJ to the distal end of the tumor is ≤ 30 mm for Siewert II AEG, esophagectomy or proximal gastrectomy is sufficient from the point of view of abdominal lymphadenectomy. However, a total gastrectomy should be considered for abdominal lymphadenectomy when this distance is > 50 mm.

Acute pericardial effusion representing the TNF-α-mediated severe inflammation but not the coronary artery outcome of Kawasaki disease.

OBJECTIVES: To establish the optimal inflammation control of Kawasaki disease (KD), we investigated the clinical and pathophysiological basis of pericardial effusion (PE) during the acute phase of KD. METHOD: Clinical and laboratory features of Japanese KD children with PE (PE group: n = 9) and without PE (non-PE group: n = 89) were studied retrospectively by using the medical records. Serum levels of soluble tumour necrosis factor receptor 1 (sTNFR1), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF) were assessed by enzyme-linked immunosorbent assays (ELISAs). RESULTS: PE group patients had coronary artery lesions (CALs) more frequently than non-PE group patients during the acute phase of KD (33% vs. 5.6%, p = 0.024). PE patients also showed lower levels of haemoglobin (p < 0.01) and serum albumin (p < 0.01) and higher platelet counts (p = 0.013) than non-PE patients. The proportion of neurological symptoms, but not other manifestations, in the PE group was higher than in the non-PE group (p = 0.022). All patients survived free from coronary artery aneurisms. Serum levels of sTNFR1, but not the other cytokines, in the PE group were higher than those in the non-PE group (p < 0.001). The sTNFR1 levels correlated positively with C-reactive protein (CRP) (r = 0.30, p = 0.019) or total bilirubin (r = 0.40, p < 0.01) levels. CONCLUSIONS: Acute PE in KD patients indicated the severity of TNF-mediated vascular inflammation and concurrent CALs. According to the progression, these patients might need more targeted therapy of anti-inflammation for a better coronary outcome.

MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer.

BACKGROUND: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. METHODS: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. RESULTS: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. CONCLUSIONS: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.

Incorporation of apical lymph node status into the seventh edition of the TNM classification improves prediction of prognosis in stage III colonic cancer.

BACKGROUND: The node classification outlined in the seventh edition of the TNM classification is based solely on the number of metastasized lymph nodes. This study examined the prognostic value of apical lymph node (ALN) metastasis and the additional value of incorporating ALN status into a risk model based on the seventh edition. METHODS: This was a cohort study of patients with stage III colonic cancer who underwent tumour resection with dissection of regional (including apical) lymph nodes at 71 hospitals across Japan between 2000 and 2002. The main exposure was pathologically confirmed ALN metastasis, and the primary endpoint was cancer-specific death. RESULTS: ALN metastasis was present in 113 (8·3 per cent) of 1355 patients. During 5356 patient-years of follow-up (median 5·0 years), 221 instances (16·3 per cent) of cancer-specific death were observed. After adjustment for tumour and node classification (as described in the seventh edition of the TNM classification) and other prognostic factors, ALN metastasis was found to be independently associated with cancer-specific death (hazard ratio 2·29, 95 per cent confidence interval (c.i.) 1·49 to 3·52). Incorporation of ALN metastasis into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for cancer-specific death (difference in concordance index 0·0146, 95 per cent c.i. 0·0030 to 0·0262) and risk reclassification for cancer-specific death at 5 years (category-free net reclassification improvement 19·4 (95 per cent c.i. 5·0 to 33·4) per cent). CONCLUSION: Assessment of ALN metastasis provided independent prognostic information beyond that achievable with the seventh edition of the TNM classification in patients with stage III colonic cancer.

CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma.

BACKGROUND: Cancer stem cells (CSCs) are responsible for treatment failure. However, their identification and roles in resistance are not well established in head and neck squamous cell carcinoma (HNSCC). METHODS: Three HNSCC cell lines (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell surface antigens were analysed by LyoPlate, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. RESULTS: CD10, CD15s, CD146 and CD282 were upregulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. Isolation mediated by FACS revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. CONCLUSIONS: CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory HNSCC.

Diagnostic value of computed tomography for staging of clinical T1 gastric cancer.

BACKGROUND: T1 gastric cancer can be diagnosed only by endoscopy and is almost curable by local treatment. It has been unclear how a multidetector-row computed tomography (CT) evaluation is valuable for clinical T1 patients. METHODS: Patients with clinical T1 disease, as diagnosed by endoscopy and treated with endoscopic submucosal dissection (ESD) or surgery between October 2000 and October 2007, were examined. The efficacy of CT was evaluated by the reversal rate of endoscopic T1 by CT, the incidence of clinical M1 disease, and the accuracy of diagnosing pathological N+ disease in patients who received surgery. To confirm metachronous distant and nodal metastases, the disease-free survival (DFS) also was evaluated. RESULTS: A total of 761 patients, 236 treated by ESD and 525 treated with surgery, were examined. None of the patients had an endoscopic diagnosis of clinical T1 reversed by CT. No clinical M1 disease was found. Among the 525 patients who underwent surgery, 8 showed clinical N+ disease (1.5 %), while 47 demonstrated pathological N+ disease (8.9 %). The accuracy, sensitivity, specificity, positive predictive value, and negative predictive values were 90.3, 4.3, 98.7, 25, and 91.3 %, respectively. The 5-year DFS rate was 93.6 % (95 % confidence interval 91.4-95.8 %). CONCLUSIONS: The present study suggests that diagnostic value of CT is limited for staging of clinical T1 gastric cancer patients, because the reversal rate of endoscopic T1 by CT was very low, clinical M1 disease was rare, the diagnosis of N+ status was unreliable, and metachronous M1 and N+ findings were rare.

Male sexual function after laparoscopic total mesorectal excision.

AIM: The aim of this prospective study was to clarify the frequency of male sexual dysfunction after laparoscopic total mesorectal excision (LTME) and to examine the relationship between pelvic autonomic nerve (PAN) preservation status and functional outcomes. METHOD: Candidates for LTME were included in this study. PAN preservation status after LTME was examined in detail by video review. Patients completed a functional questionnaire (the International Index of Erectile Function) before and 3, 6 and 12 months after the operation. RESULTS: Twenty-six patients who underwent LTME were assessable. Detailed video reviews identified inadvertent PAN damage during surgery. PAN injury was observed in 11 cases (41%), including eight cases (32%) of inadvertent PAN damage (incomplete preservation group). There was a trend toward increasing inadvertent PAN injury rate in patients with high body mass index and large tumours. The results from all patients who underwent LTME showed no deterioration in total International Index of Erectile Function or its domain scores 12 months after surgery. In the incomplete preservation group, these scores temporarily decreased (3 and 6 months after surgery), but such deterioration was not observed in the complete preservation group. Most of the 12 patients with potentially active erectile function before the operation recovered this function, and only one patient (7%) with PAN injury was still judged as inactive 12 months after surgery. CONCLUSION: The proportion of patients with sexual dysfunction after LTME is low. With the enhanced visibility of the laparoscope, inadvertent PAN injury was detected in a significant number of cases and associated with transient deterioration of sexual function.

Prognostic significance of metabolic response by positron emission tomography after neoadjuvant chemotherapy for resectable malignant pleural mesothelioma.

BACKGROUND: To select optimal candidates for extrapleural pneumonectomy (EPP), we retrospectively evaluated the usefulness of metabolic response by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemotherapy to predict prognosis for patients with resectable malignant pleural mesothelioma (MPM) who underwent EPP in a multicenter study. PATIENTS AND METHODS: We carried out high-resolution CT (HRCT) and FDG-PET/CT before and after neoadjuvant platinum-based chemotherapy on 50 patients with clinical T1-3 N0-2 M0 MPM who underwent EPP ± postoperative hemithoracic radiotherapy. A decrease of ≥30% in the tumor maximum standardized uptake value (SUVmax) was defined as a metabolic responder. The radiologic response using the modified RECIST or metabolic response and surgical results were analyzed. RESULTS: The median overall survival (OS) from diagnosis was 20.5 months. Metabolic responders significantly correlated to OS with median OS for metabolic responders not reached versus 18.7 months for non-responders. No correlation was observed between OS and radiologic response with median OS for radiologic responders and non-responders. Based on the multivariate Cox analyses, decreased SUVmax and epithelioid subtype were significantly independent factors for OS. CONCLUSIONS: The metabolic response after neoadjuvant chemotherapy is an independent prognostic factor for patients with resectable MPM. Patients with metabolic responder or epithelioid subtype may be good candidates for EPP.

Impact of oesophagectomy on physical fitness and health-related quality of life in patients with oesophageal cancer.

Although several studies have reported the impact of oesophagectomy on health-related quality of life (HRQOL), none has objectively assessed its impact on physical fitness. This study aimed to evaluate the impact of oesophagectomy on physical fitness and HRQOL in patients with oesophageal cancer. In this prospective study, we investigated 30 consecutive patients with newly diagnosed resectable oesophageal cancer who were scheduled to receive either neoadjuvant chemotherapy followed by surgery or surgery alone. The primary end-points were change from baseline in two measures of physical fitness (knee-extensor muscle strength and 6-min walking distance) after oesophagectomy. The secondary end-point was change from baseline in HRQOL measured with the European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire with 30 items (EORTC QLQ-C30). Physical fitness was significantly lower after oesophagectomy than before oesophagectomy (P < 0.001). With regard to HRQOL, there was a significant pre- to post-oesophagectomy change in most of the scales. In the multiple regression analysis, the change in 6-min walking distance was the only significant variable affecting the change in physical functional score on the EORTC QLQ-C30 (P = 0.032). In conclusion, oesophagectomy adversely affects physical fitness and HRQOL in patients with oesophageal cancer. Six-minute walking distance may be a good indicator of HRQOL shortly after oesophagectomy.