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.

Revisiting the Prognostic Impact of Family History in Colorectal Cancer by Retrospective Propensity Score Matching.

BACKGROUND/AIM: Family history of colorectal cancer (CRC) is a known risk factor for CRC. However, its prognostic value in patients with CRC remains controversial. This study aimed to clarify the prognostic impact of a family history of CRC. PATIENTS AND METHODS: We retrospectively reviewed the database from 1978 to 2018 and enrolled 3,655 consecutive patients with CRC. We investigated the clinicopathological factors of patients with CRC with and without a family history. After propensity score matching, we performed a survival analysis of patients with CRC with and without a family history. RESULTS: Patients with CRC with a family history of CRC had a young onset (63.2 and 65.9; p<0.001), were more likely to be female (54.3% and 49.7%; p=0.042), had less symptomatic disease (76.9% and 80.8%; p=0.008), were more likely to have right-sided colon cancer (27.5% and 26.1%), and had less distant metastases (11.3% and 14.9%; p=0.023) and multiple CRCs (10.2% and 7.8%) compared with those without a family history of CRC. Prior to propensity score matching, CRC-specific survival analysis showed that a family history of CRC was a good prognostic factor (p=0.022). After propensity score matching, survival curves overlapped between the two groups. CONCLUSION: Patients with CRC with a family history of CRC had specific clinicopathological features including younger onset, female sex, proximal colon location, fewer symptoms, smaller number of distant metastases, likelihood of multiple diseases, and earlier cancer stage. Family history of CRC in patients with CRC was not a prognostic factor.

Relationship between prognostic impact of N3 lymph node metastasis at the root of the feeding artery and location of colon cancer.

PURPOSE: To determine whether N3 nodal involvement predicts outcomes and whether its prognostic implications vary with tumor location in patients with Stage III colon cancer (CC). METHODS: We defined N3 as lymph node metastases near the bases of the major feeding arteries. We retrospectively examined recurrence rates and patterns by tumor location and sites of lymph node metastases in 57 patients with N3 CC who had undergone curative resections between January 2000 and March 2019. Survival analysis was performed to compare the prognoses of patients with and without N3 lymph node metastasis. RESULTS: Most N3 patients had large tumors (T ≥ 3); five had T2 disease. Recurrence occurred quickly in one patient with T2N3M0 disease. Multivariate survival analysis demonstrated that N3 lymph node metastasis is an independent predictor of poor prognosis in Stage III CC patients (P < 0.001). Categorizing N3 patients according to UICC-TNM staging system does not stratify risk of recurrence (P = 0.970). To investigate the impact of tumor location on recurrence risk, we classified N3 CC into two subtypes according to tumor location: metastasis at the base of the superior mesenteric artery in right-sided CC and inferior mesenteric artery in left-sided CC. The former was found to have a statistically significant poorer prognosis than the latter (P = 0.091). CONCLUSION: N3 is a robust prognostic marker in CC patients. Recurrence risk varies by tumor location. N3 right-sided CCs with lymph node metastasis at the base of the superior mesenteric artery have poorer prognoses than do N3 left-sided CCs.

Reliability, validity, and responsiveness of the Japanese version of the EORTC QLQ-ELD14 in evaluating the health-related quality of life of elderly patients with cancer.

PURPOSE: This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years. METHODS: The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic. RESULTS: In both age groups, the proportion of missing items was low (< 3%). Cronbach's α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item ("maintaining purpose") of the EORTC QLQ-ELD14 worsened (- 6.14 ± 29.20, standard response of mean > 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the "global health status/QOL" and "summary score" of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%. CONCLUSION: The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer.

PTPN3 Could Βe a Therapeutic Target of Pancreatic Cancer.

BACKGROUND/AIM: Recently, protein tyrosine phosphatase non-receptor type 3 (PTPN3) has gained attention. However, the role of PTPN3 in cancer has not been fully elucidated. In the present study, we analyzed the role of PTPN3 in pancreatic cancer and investigated whether PTPN3 could be a new therapeutic target for pancreatic cancer. MATERIALS AND METHODS: Two pancreatic ductal adenocarcinoma (PDAC) cell lines were used as target cells. Cell proliferation was investigated using cell counting and a xenograft mouse model. Migration and invasion were analyzed using Transwell inserts. Activation-related signaling molecules were examined by western blotting. RESULTS: PTPN3 contributes to the proliferation, migration, and invasion of PDAC cells in vitro. PTPN3 promotes tumor growth in a mouse xenograft model, an action mediated partially through the MAPK pathway. CONCLUSION: PTPN3 could be a new therapeutic target for pancreatic cancer.

Cross-sectional area of psoas muscle as a predictive marker of anastomotic failure in male rectal cancer patients: Japanese single institutional retrospective observational study.

PURPOSE: Preoperative sarcopenia worsens postoperative outcomes in various cancer types including colorectal cancer. However, we often experienced postoperative anastomotic leakage in muscular male patients such as Judo players, especially in rectal cancer surgery with lower anastomosis. It is controversial whether the whole skeletal muscle mass impacts the potential for anastomotic failure in male rectal cancer patients. Thus, the purpose of this study was to clarify whether skeletal muscle mass impacts anastomotic leakage in rectal cancer in men. METHODS: We reviewed the medical charts of male patients suffering from rectal cancer who underwent colo-procto anastomosis below the peritoneal reflection without a protective diverting stoma. We measured the psoas muscle area and calculated the psoas muscle index. RESULTS: One hundred ninety-seven male rectal cancer patients were enrolled in this study. The psoas muscle index was significantly higher in patients with anastomotic leakage (P<0.001). Receiver operating characteristic curve determined the optimal cut-off value of the psoas muscle index for predicting anastomotic leakage as 812.67 cm2/m2 (sensitivity of 60% and specificity of 74.3%). Multivariate analysis revealed that high psoas muscle index (risk ratio [RR], 3.933; P<0.001; 95% confidence interval [CI], 1.917-8.070) and super low anastomosis (RR, 2.792; P=0.015; 95% CI, 1.221-6.384) were independent predictive factors of anastomotic leakage. CONCLUSION: This study showed that male rectal cancer patients with a large psoas muscle mass who underwent lower anastomosis had a higher rate of postoperative anastomotic leakage.

Cancer therapy that targets the Hedgehog signaling pathway considering the cancer microenvironment (Review).

Recently, the cancer microenvironment (CME) has received significant attention. At the local site of the tumor, cancer progression is affected by secreted cytokines and conditions derived from the CME and stimulation by cancer­induced cytokines in an autocrine manner. The CME is characterized by various types of conditions, such as hypoxia, inflammation stimulation, and angiogenesis, and contains various components, such as reactive oxygen species, cancer­associated fibroblasts, infiltrated immune cells, exosomes, and cancer stem cells (CSCs). These conditions and components complicate the progression of cancer. The Hedgehog (HH) signaling pathway is a morphogenesis signaling pathway that is reactivated in some cancers. In these cancers, reactivated HH signaling is involved in the induction of the malignant phenotype. HH signaling is also activated under hypoxic conditions and is considered to be strongly correlated with the CME, including the induction of cancer fibrosis and maintenance of CSCs. The aim of the present review was to elucidate a cancer therapy that targets HH signaling by considering the CME, particularly focusing on hypoxia.

Long-term effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in rectal cancer.

BACKGROUND: The addition of lateral pelvic lymph node dissection (LPLND) in rectal cancer surgery has been reported to increase the incidence of post-operative urinary retention. Here, we assessed the predictive factors and long-term outcomes of urinary retention following laparoscopic LPLND (L-LPLND) with total mesorectal excision (TME) for advanced lower rectal cancer. METHODS: This retrospective single-institutional study reviewed post-operative urinary retention in 71 patients with lower rectal cancer who underwent L-LPLND with TME. Patients with preoperative urinary dysfunction or who underwent unilateral LPLND were excluded. Detailed information regarding patient clinicopathologic characteristics, post-void residual urine volume, and the presence or absence of urinary retention over time was collected from clinical and histopathologic reports and telephone surveys. Urinary retention was defined as residual urine > 100 mL and the need for further treatment. RESULTS: Post-operative urinary retention was observed in 25/71 patients (35.2%). Multivariate analysis revealed that blood loss ≥ 400 mL [odds ratio (OR) 4.52; 95% confidence interval (CI) 1.24-16.43; p = 0.018] and inferior vesical artery (IVA) resection (OR 8.28; 95% CI 2.46-27.81; p < 0.001) were independently correlated with the incidence of urinary retention. Furthermore, bilateral IVA resection caused urinary retention in more patients than unilateral IVA resection (88.9% vs 47.1%, respectively; p = 0.049). Although urinary retention associated with unilateral IVA resection improved relatively quickly, urinary retention associated with bilateral IVA resection tended to persist over 1 year. CONCLUSION: We identified the predictive factors of urinary retention following L-LPLND with TME, including increased blood loss (≥ 400 mL) and IVA resection. Urinary retention associated with unilateral IVA resection improved relatively quickly. L-LPLND with unilateral IVA resection is a feasible and safe procedure to improve oncological curability. However, if oncological curability is guaranteed, bilateral IVA resection should be avoided to prevent irreversible urinary retention.

TrkB/BDNF Signaling Could Be a New Therapeutic Target for Pancreatic Cancer.

BACKGROUND/AIM: Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells. MATERIALS AND METHODS: Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors. RESULTS: All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells. CONCLUSION: TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.

High frequency of bone recurrence as an initial recurrence site after radical surgery in T1N3 gastric cancer: a propensity score matching analysis.

PURPOSE: T1 gastric cancer (GC) with seven or more metastatic lymph nodes is extremely rare, and very few clinical studies have been conducted to evaluate the clinicopathological features of their recurrence. METHODS: We retrospectively analyzed the outcomes of T1 GC and T2-4 GC patients who had multiple nodal metastases after radical surgery from 2006 to 2020. Propensity score matching was performed to compare the two groups of patients. RESULTS: After propensity score matching, 18 of 22 patients in the T1 group and 36 of 144 patients in the T2-4 group were selected. Recurrence occurred in six patients (33.3%) in the T1 group. In the T1 group, the most common site of initial recurrence was bone (15.0%). The prevalence of bone recurrence was significantly higher in the T1 group than in the T2-4 group (P = 0.02). The median interval time between radical surgery and bone recurrence was 24 months, and the median survival time after bone recurrence was 14 months. CONCLUSION: Bone recurrence was more frequently identified as an initial recurrence site in T1 GC cases with multiple metastases after radical surgery compared with that in T2-4 GC cases. Careful attention should be paid to postoperative bone recurrence in the long-term postoperative course of these patients.

Predictive factors associated with relapse of stage II/III colon cancer treated with peroral anti-cancer agents in the adjuvant setting.

Postoperative adjuvant chemotherapy for patients with stage III colon cancer (CC) is regarded as the standard treatment worldwide for outcome improvement and relapse prevention. Similarly, high-risk stage II CC requires adjuvant chemotherapy because of its high recurrence rate. Previous randomized controlled trials showed that oxaliplatin (OX), in addition to fluorinated pyrimidine-based therapy for patients with stage II/III CC, significantly improves cancer survival but it remains controversial as to which patient groups should receive OX-containing regimens. Among 1,150 consecutive patients who underwent curative resection for stage II/III CC between 2009 and 2016 at two tertiary hospitals, 349 patients treated with only peroral (PO) fluorinated pyrimidine-based chemotherapy and 149 patients who received fluorinated pyrimidine-based chemotherapy with OX as adjuvant chemotherapy were retrospectively reviewed. The primary outcome was recurrence-free survival (RFS). Clinicopathological factors were more advanced in patients treated with OX than in patients treated only with PO fluorinated pyrimidine agents. Multivariate analysis for 5-year RFS showed that T4 [hazard ratio (HR), 2.947; P=0.0001], N2 (HR, 2.704; P=0.0075), vessel or lymphatic invasion (HR, 1.675; P=0.0437) and high cancer antigen (CA)19-9 (HR 3.367, P=0.0002) levels were independent risk factors of cancer relapse. Propensity score matching analysis was performed to match clinicopathological differences between the PO and OX groups. After matching, subgroup analysis of the patients showed that greater effects of OX on cancer survival were observed in patients in the OX group with high CA19-9 levels and tended to be associated with T4 and N2 compared with the PO group. Thus, OX-containing regimens should be recommended for patients with CC with these factors in an adjuvant setting.

N-acetyl cysteine induces quiescent-like pancreatic stellate cells from an active state and attenuates cancer-stroma interactions.

BACKGROUND: Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy, and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was habitually used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions. METHOD: We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness, viability, and oxidative level in PSCs and PCCs after NAC treatment. Using an indirect co-culture system, we investigated changes in viability, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and Pioglitazone were evaluated in PSCs and PCCs. In vivo, we co-transplanted KPC-derived organoids and PSCs to evaluate the effects of NAC and Pioglitazone's combination therapy on subcutaneous tumor formation and splenic xenografted mouse models. RESULTS: In vitro, NAC inhibited the viability, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced oxidative stress level and expression of α-SMA, collagen type I in PSCs, which apparently present a quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the viability, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, NAC and Pioglitazone's combination suppressed tumor growth and liver metastasis with fewer stromal components and oxidative stress level. CONCLUSION: NAC suppressed activated PSCs and attenuated cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment.

Risk factors for postoperative pneumonia after laparoscopic gastrectomy in patients aged 75 years and over with gastric cancer.

INTRODUCTION: The proportion of patients aged 75 years and over who undergo minimally invasive surgery for gastric cancer is increasing. However, the safety and feasibility of laparoscopic gastrectomy (LG) in this age group is controversial. This study aimed to evaluate whether LG is safe and effective in patients aged 75 years and over. METHODS: The study included 728 patients with early and advanced gastric cancer who underwent curative LG between 2009 and 2017; 166 of these patients (22.8%) were aged 75 or over. All surgeries were performed laparoscopically. Selected clinical factors were compared between the 166 patients aged 75 years and over and the 562 patients aged under 75 years. RESULTS: There were significant differences in presence of comorbidity, respiratory function and American Society of Anesthesiologists physical status scores between the older and younger groups. The older patients more frequently developed complications than the younger ones, particularly postoperative pneumonia. According to multivariate analyses of all participants, age, chronic obstructive pulmonary disease (COPD), and D2 lymphadenectomy were independent risk factors for postoperative pneumonia. Advanced stage and D2 lymphadenectomy were independent risk factors in the older group, whereas only COPD was an independent risk factor in the younger group. CONCLUSIONS: LG for gastric cancer can be safely performed in patients aged over 75 years with an acceptable complication rate. However, the present data suggest that care should be taken in selecting LG with D2 lymphadenectomy to treat advanced cancer in these patients because the risk of postoperative complications, especially postoperative pneumonia, increases.

Thoracoscopic surgery combined with endoscopic creation of a submucosal tunnel for a large complicated esophageal leiomyoma.

BACKGROUND: The standard surgical method for symptomatic submucosal tumors (SMTs) or tumors with unclear biological behavior is enucleation. Minimally invasive approaches are usually considered appropriate for surgical enucleation; thus, thoracoscopic and laparoscopic enucleation is performed widely and safely. However, it is sometimes difficult to enucleate large and complicated esophageal tumors using thoracoscopic surgery, and even if rare, there is the risk of requiring thoracotomy or esophagectomy. In the present case, we enucleated a large and complicated leiomyoma safely using a new combined method with endoscopic and thoracoscopic procedures. CASE PRESENTATION: A 42-year-old woman presented to our hospital for a detailed examination of an abnormal finding in her health check-up chest X-ray images. She complained of upper abdominal pain after eating, and computed tomography revealed an esophageal tumor measuring 60 mm in length surrounding her lower thoracic esophagus. Esophagogastroduodenoscopy revealed a huge complicated SMT at the esophagogastric junction. Cytological examination with endoscopic ultrasound-guided fine-needle aspiration showed that the tumor was a leiomyoma. To enucleate this large and complicated esophageal SMT safely and without damaging the esophageal mucosa, we performed endoscopic and thoracoscopic procedures. We created a submucosal tunnel, endoscopically, and then performed thoracoscopic surgery to enucleate the tumor completely from the esophageal muscularis. Using these combined procedures, we were able to easily mobilize even a complicated tumor of this size from the mucosa and completed the surgery thoracoscopically without difficulty. As a result, the tumor was dissected safely with a minimal defect in the muscularis and without damaging the mucosa. Finally, we closed the defect in the esophageal muscularis with continuous sutures, thoracoscopically, and closed the entry of the submucosal tunnel using clips, endoscopically. CONCLUSIONS: Using these combined procedures, we safely enucleated a huge complicated esophageal SMT. The increased mobility of the tumor after creating the submucosal tunnel contributed to the minimal defect in the muscular layer and prevented injury to the esophageal mucosa, possibly leading to fewer postoperative complications such as esophageal stenosis and local infection.

Influence of endoscopic resection on additional laparoscopic distal gastrectomy: a propensity score-matching analysis.

PURPOSE: There is no definite evidence of the feasibility and safety of laparoscopic distal gastrectomy (LDG) for patients who have undergone incomplete endoscopic resection (ER). We investigated the influence of ER prior to LDG by a propensity score matching analysis. METHODS: We retrospectively analyzed the outcomes of gastric cancer patients who underwent LDG with or without prior ER from 2000 to 2014. Propensity score matching was performed to compare the two groups of patients. RESULTS: After matching, 47 patients in the ER group and 94 patients in the non-ER group were selected from a total of 365 patients. A residual tumor was observed in 10 of 47 patients (21.3%). The mean number of dissected lymph nodes in the non-ER group (39.4 ± 14.5) was higher than that in the ER group (31.7 ± 13.5) (P = 0.003). However, other perioperative data, such as the operation time and blood loss volume were similar. The complication rate of the ER group (17.0%) and the non-ER group (9.6%) did not differ to a statistically significant extent (P = 0.2). Among these patients, 6 died during the 5-year follow-up period, but no patients showed signs of recurrence. CONCLUSION: ER prior to surgical resection showed no significant influence on postoperative complications or mortality. LDG can be safely performed to achieve radical resection after incomplete ER.

Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer.

Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient's prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition.

Laparoscopic spacer placement for recurrent sacral chordoma before carbon ion radiotherapy: A case report.

Recently, several scholars have demonstrated the efficacy of carbon ion radiotherapy (CIRT). To treat abdominal or pelvic tumors by CIRT, it is necessary to separate the tumor from the adjacent organs. Surgical placement of a GORE-TEX sheet as a spacer has been reported as a separation method. Usually, surgical spacer placement is done by open surgery. Here, we report a case of surgical spacer placement undertaken by a "pure" laparoscopic procedure. A 47-year-old man with recurrent sacral chordoma was referred for surgical spacer placement before CIRT. Laparoscopic dissection of the rectum and placement of a GORE-TEX sheet as a spacer were successfully performed. Surgical spacer placement by a pure laparoscopic procedure was safe and effective, and it seems to play an important part before CIRT.

Numerous lymph node metastases in early gastric cancer without preoperatively enlarged lymph nodes: a case report.

BACKGROUND: According to the 2018 Japanese gastric cancer treatment guidelines (ver. 5), a reduced extent of lymphadenectomy (D1 or D1+) is indicated for cT1 N0 tumors that do not meet the criteria for endoscopic resection. However, early gastric cancer with multiple lymph node metastases is not unknown, and cases have been reported. We report a case of a patient with early gastric cancer and numerous nodal metastases who underwent laparoscopic proximal gastrectomy based on a preoperative diagnosis of T1 N0. CASE PRESENTATION: A 69-year-old woman underwent emergent endoscopic hemostasis for massive hematemesis of the stomach, and endoscopic examination showed ulceration with a visible vessel. Pathological biopsy examination of the ulcer identified poorly differentiated adenocarcinoma with signet ring cells. The patient was diagnosed with early gastric cancer that was not indicated for endoscopic resection because of the ulceration and histological type. Endoscopic ultrasound showed that the third layer was poorly demarcated at the ulcer scar, indicating invasion to the submucosal layer. Computed tomography did not reveal enlarged lymph nodes or distant metastasis. The preoperative diagnosis was early gastric cancer of the fundus without nodal metastasis, and laparoscopic proximal gastrectomy with D1+ lymphadenectomy was performed. The initial postoperative pathological diagnosis was intramucosal carcinoma without lymphovascular invasion; however, the presence of 26 lymph node metastases was revealed unexpectedly. Additional pathological examination of more resected specimens transected every 2-3 mm revealed that only one lesion contained a small number of cancer cells in the lymphatic duct below the muscularis mucosa. CONCLUSIONS: We report a case of early gastric cancer with 26 nodal metastases in which lymph node involvement was not identified prior to surgery. These findings indicate that the extent of lymphadenectomy and the surgical procedure should be carefully decided even in cT1 N0 early gastric cancer when several risk factors for lymph node metastasis are present.

Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer: In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry.

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85-11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04-196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.

Short-term and long-term outcomes of indigo naturalis treatment for inflammatory bowel disease.

BACKGROUND AND AIM: Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease. METHODS: Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan-Meier method. Overall adverse events (AEs) during follow-up were also analyzed. RESULTS: Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non-responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow-up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient. CONCLUSIONS: Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment.