Laparoscopic colectomy for patients with poor American Society of Anesthesiology classifications.

INTRODUCTION: The American Society of Anesthesiologists (ASA) classification is used to assess the fitness of a patient for surgery. Whether laparoscopic surgery is appropriate for colorectal cancer patients with poor ASA performance status (PS) remains unclear. METHODS: Among 4585 patients who underwent colorectal surgery between 2016 and 2023, this study retrospectively reviewed all 458 patients with ASA-PS ≥3. Patients were divided into two groups: patients treated by open surgery (O group, n = 80); and patients treated by laparoscopic surgery (L group, n = 378). We investigated the impact of surgical approach on postoperative complications in patients with colorectal cancer and ASA-PS ≥3. RESULTS: Operation time was longer (170 min vs. 233 min, p < .001), blood loss was less (156 mL vs. 23 mL, p < .001), postoperative complications were less frequent (40.0% vs. 25.1%, p = .008), and hospital stay was shorter (23 days vs. 14 days, p < .001) in L group. Univariate analysis revealed rectal cancer, open surgery, longer operation time, and blood loss as factors significantly associated with postoperative complications. Multivariate analysis revealed open surgery (odds ratio [OR] 2.100, 95% confidence interval [CI] 1.164-3.788; p = .013) and longer operation time (OR 1.747, 95% CI 1.098-2.778; p = .018) as independent predictors of postoperative complications. CONCLUSION: Laparoscopic surgery provides favorable outcomes for colorectal cancer patients with poor ASA-PS.

Prognostic impact of postoperative management by an intensive care unit intensivist after colonic perforation.

PURPOSE: Postoperative management for colonic perforation is an important prognostic factor, but whether intensivists perform postoperative management varies between institutions. METHODS: We investigated 291 patients with colonic perforation between 2018 and 2022. Patients were divided into those managed by an intensivists (ICU group; n = 40) and those not managed by an intensivists (non-ICU group; n = 251). We examined how management by intensivists affected prognosis using inverse probability weighting, and clarified which patients should consult an intensivists. RESULTS: The ICU group showed a significantly higher shock index (1.15 vs. 0.75, p < 0.01), higher APACHE II score (16.0 vs. 10.0, p < 0.001), and more severe comorbidities (Charlson Comorbidity Index 5.0 vs. 1.0, p < 0.001) and general peritonitis (85% vs. 38%, p < 0.001). Adjusted risk differences were - 24% (-34% to -13%) for 6-month mortality rate. Six-month mortality was improved by ICU intensivist management in patients with general peritonitis (risk difference - 22.8; 95% confidence interval - 34 to -11); APACHE II score ≥20 (-0.79; -1.06 to -0.52); lactate ≥1.6 (-0.38; -0.57 to -0.29); shock index ≥1.0 (-40.01; -54.87 to -25.16); and catecholamine index ≥10 (-41.16; -58.13 to -24.19). CONCLUSIONS: Intensivists were involved in treating patients in poor general condition, but prognosis was extremely good. Appropriate case consultation with intensivists is important.

The C-reactive protein-albumin-lymphocyte (CALLY) index is a useful predictor of postoperative complications in patients with a colonic stent for obstructive colorectal cancer: a Japanese multicenter study.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel score that offers a good reflection of nutritional status, inflammatory response, and immune system status. The CALLY index is reported to correlate with the prognosis of various carcinomas. The purpose of the present study was to investigate the association between the CALLY index and the short-term prognosis of obstructive colorectal cancer managed with a colonic stent. METHODS: The subjects of this retrospective study were 263 patients who underwent colorectal resection after colonic stenting for obstructive colorectal cancer between 2016 and 2023. Patients were classified into a group with a low CALLY index (CALLY-L group, n = 85) and a group with a high (CALLY-H group, n = 178) CALLY index. RESULTS: The CALLY-L group had greater blood loss (53 mL vs 20 mL, p = 0.002) and higher poor performance status (PS3; 20% vs 10.1%, p = 0.033), open surgery (21.2% vs 7.3%, p = 0.001), distant metastases (41.2% vs 20.8%, p = 0.01), and postoperative complications (30.6% vs. 18.5%, p = 0.039) than the CALLY-H group. Multivariate analysis identified a prolonged operative time (odds ratio 1.983, 95% confidence interval 1.013-3.881; p = 0.045), greater blood loss (odds ratio 2.572, 95% confidence interval 1.291-5.129; p = 0.007) and a low CALLY index (odds ratio 1.961, 95% confidence interval 1.013-3.795; p = 0.045) as independent predictors of complications. CONCLUSION: The CALLY index may be a useful predictor of postoperative complications of obstructive colorectal cancer.

Effect of the lymphocyte-to-monocyte ratio on the prognosis of patients with obstructive colorectal cancer with a colonic stent: a retrospective multicenter study in Japan.

PURPOSE: The prognostic value of the lymphocyte-to-monocyte (LMR) ratio has been reported for various cancers, including colorectal cancer (CRC). The insertion of colonic stents is considered effective for patients with surgically indicated obstructive CRC, but their LMR can vary depending on factors such as inflammation associated with stent dilation and improvement of obstructive colitis. However, the usefulness of the LMR in patients with obstructive CRC and colonic stents and the optimal timing for its measurement remain unclear. We conducted this study to investigate the relationship between the pre-stent LMR and the mid-term prognosis of patients with obstructive CRC and stents as a bridge to surgery (BTS). METHODS: The subjects of this retrospective multicenter study were 175 patients with pathological stage 2 or 3 CRC. Patients were divided into a low pre-stent LMR group (n = 87) and a high pre-stent LMR group (n = 83). RESULTS: Only 3-year relapse-free survival differed significantly between the low and high pre-stent LMR groups (39.9% vs. 63.6%, respectively; p = 0.015). The pre-stent LMR represented a prognostic factor for relapse-free survival in multivariate analyses (hazard ratio 2.052, 95% confidence interval 1.242-3.389; p = 0.005), but not for overall survival. CONCLUSIONS: A low pre-stent LMR is a prognostic factor for postoperative recurrence in patients with obstructive CRC and a colonic stent as a BTS.

Risk factors for pulmonary complications after colorectal cancer surgery: a Japanese multicenter study.

PURPOSE: Pulmonary complications (PC) are a serious condition with a 20% mortality rate. However, few reports have examined risk factors for PC after colorectal surgery. This study investigated the frequency, characteristics, and risk factors for PC after colorectal cancer surgery. METHODS: Between January 2016 and December 2022, we retrospectively reviewed 3979 consecutive patients who underwent colorectal cancer surgery in seven participating hospitals. Patients were divided into patients who experienced PC (PC group, n = 54) and patients who did not (non-PC group, n = 3925). Clinical and pathological features were compared between groups. RESULTS: Fifty-four patients (1.5%) developed PC, of whom 2 patients (3.7%) died due to PC. Age was greater (80 years vs 71 years; p < 0.001), frequency of chronic obstructive pulmonary distress was greater (9.3% vs 3.2%; p = 0.029), performance status was poorer (p < 0.001), the proportion of underweight was higher (42.6% vs 13.4%, p < 0.001), frequency of open surgery was greater (24.1% vs 9.3%; p < 0.001), and blood loss was greater (40 mL vs 22 mL; p < 0.001) in the PC group. Multivariate analysis revealed male sex (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.176-3.986; p = 0.013), greater age (OR 3.180, 95%CI 1.798-5.624; p < 0.001), underweight (OR 3.961, 95%CI 2.210-7.100; p < 0.001), and poorer ASA-PS (OR 3.828, 95%CI 2.144-6.834; p < 0.001) as independent predictors of PC. CONCLUSION: Our study revealed male sex, greater age, underweight, and poorer ASA-PS as factors associated with development of PC, and suggested that pre- and postoperative rehabilitation and pneumonia control measures should be implemented for patients at high risk of PC.

Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models.

Background: Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion. Objective: To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment. Methods: dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed. Results: Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin ß1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs. Conclusion: We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.

Short- and Long-term Outcomes After Colonic Stent Insertion as a Bridge to Surgery in Elderly Colorectal Cancer Patients.

BACKGROUND/AIM: Colonic stents have been inserted as a bridge to surgery in patients with resectable colorectal cancer, allowing bowel decompression for systemic assessment and better preparation to avoid stoma construction. However, reports of short- and long-term prognoses for elderly patients remain limited. PATIENTS AND METHODS: This retrospective study reviewed 175 consecutive patients who underwent colonic stent insertion for bowel obstruction followed by curative colectomy. Patients were divided into those >80 years old (Old, n=49) and those <80 years old (Young, n=126). After propensity score matching, 41 patients in each group matched. RESULTS: Before matching, performance status was poorer (p<0.001), postoperative complication rate was higher (p=0.009), adjuvant chemotherapy rate was lower (p<0.001), and hospital stay was longer (p<0.001) in the Old group. After matching, adjuvant chemotherapy rate was lower (9.8% vs. 39.0%; p=0.003) and hospital stay was longer (14 vs. 12 days; p=0.029) in the Old group. Five-year relapse-free survival (42.9% vs. 68.8%; p=0.200), overall survival (66.3% vs. 87.7%; p=0.081), and cancer-specific survival (68.2% vs. 87.7%; p=0.129) rates were comparable between groups. CONCLUSION: Colorectal resection after colonic stent insertion is useful for elderly patients, with potential to reduce postoperative complication rates and achieve good long-term results with appropriate case selection.

Impact of institutional volume on short- and long-term outcomes after laparoscopic colectomy.

INTRODUCTION: The impact of institutional volume on postoperative outcomes after laparoscopic colectomy is still being debated. This study aimed to investigate whether differences in postoperative outcomes of laparoscopic colon resection exist between high- and low-volume centers. METHODS: Data were reviewed for 1360 patients who underwent laparoscopic colectomy for colon cancer between 2016 and 2022. Patients were divided according to whether they were treated at a high-volume center (≥100 colorectal surgeries annually; n = 947) or a low-volume center (<100 colorectal surgeries annually; n = 413). Propensity score matching was applied to balance covariates and minimize selection biases that could affect outcomes. Finally, 406 patients from each group were matched. RESULTS: After matching, patients from high-volume centers showed a higher number of retrieved lymph nodes (19 vs. 17, p < .001) and more frequent involvement of expert surgeons (98.3% vs. 88.4%, p < .001). Postoperative complication rates were similar between groups (p = .488). No significant differences between high- and low-volume centers were seen in relapse-free survival (88.8% each, p = .716) or overall survival (85.7% vs. 82.8%, p = .480). CONCLUSION: The present study suggests that in appropriately educated organizations, relatively safe procedures and good prognosis may be obtained for laparoscopic colectomy cases, regardless of institutional volume.

Prognostic value of lymph node distribution after laparoscopic colectomy with Japanese D3 dissection.

PURPOSE: Positive pathologic lymph nodes in colorectal cancer represent an important prognostic indicator. Whether lymph node distribution or the number of metastatic nodes is more strongly associated with survival prediction remains controversial. METHODS: Among 3449 colorectal cancer surgeries performed at Nagasaki University Hospital and five affiliated institutions from April 2016 to March 2022, we investigated 604 patients who underwent laparoscopic radical resection and were diagnosed with pathological stage III cancer. Patients were divided into two groups according to whether they had central vessel metastasis (LND3 group, n=42) or not (LND1/2 group, n=562). After adjusting for background factors using propensity score matching, the LND3 group included 42 patients and the LND1/2 group included 40 patients. Patient background characteristics and prognosis were compared between these two groups. RESULTS: Before matching, frequencies of right-side colon cancer (64.3% vs 38.1%, p=0.001), multivisceral resection (11.9% vs 4.4%, p=0.039), clinical N2 status (40.5% vs 22.6%, p=0.032), and pathological N2 (73.8% vs 22.6%, p<0.001) were all greater, and the number of lymph nodes retrieved was higher (24 vs 19, p=0.042) in the LND3 group. After matching, no differences in any clinical factors were evident between groups. Five-year RFS (44.8% vs 77.1%, p=0.004) and OS (43.1% vs 83.2%, p<0.001) were worse in the LND3 group. Adjuvant chemotherapy improved RFS (adjuvant chemotherapy (+) vs adjuvant chemotherapy (-): 62.1% vs 27.7%, p=0.047) in the LND3 group. CONCLUSION: LND3-positive patients show poorer prognosis than LND1/2 patients and should be treated with an appropriate perioperative treatment strategy.

Risk factors for reoperation within 30 days in laparoscopic colorectal cancer surgery: A Japanese multicenter study.

INTRODUCTION: Thirty-day reoperation rate reflects short-term surgical outcomes following surgery. Laparoscopic surgery for colorectal cancer reportedly has positive effects on postoperative complications. This retrospective study investigated risk factors for 30-day reoperation rate among patients after laparoscopic colorectal cancer surgery using a multicenter database. METHODS: Participants comprised 3037 patients who had undergone laparoscopic resection of colorectal cancer between April 2016 and December 2022 at the Nagasaki University and six affiliated centers, classified into those who had undergone reoperation within 30 days after surgery (RO group; n = 88) and those who had not (NRO group; n = 2949). Clinicopathological characteristics were compared between groups. RESULTS: In the RO group, anastomotic leakage occurred in 57 patients (64.8%), intestinal obstruction in 12 (13.6%), and intraabdominal abscess in 5 (5.7%). Female patients were more frequent, preoperative treatment less frequent, body mass index (BMI) lower, operation time longer, blood loss greater, and hospital stay longer in the RO group (p < .05 each). Multivariate analysis revealed BMI (odds ratio, 0.415; 95% confidence interval, 0.218-0.787; p = .021) and poor performance status (odds ratio, 1.966; 95% confidence interval, 1.106-3.492; p = .021) as independent predictors of reoperation. CONCLUSION: Perioperative measures are warranted for patients with low BMI and poor performance status undergoing laparoscopic colorectal surgery.

Effect of adjuvant chemotherapy after curative resection of colorectal cancer peritoneal metastasis.

PURPOSE: Several guidelines have recommended surgical resection for localized peritoneal metastases, but the prognosis remains poor. In addition, the efficacy of adjuvant chemotherapy (AC) after curative resection is under debate. The present study compared long-term outcomes between curative and non-curative resection and evaluated the effects of AC after curative resection. METHODS: Using a multicenter database, we retrospectively reviewed 123 colorectal cancer patients with peritoneal metastases between April 2016 and December 2021. Of these patients, 49 underwent curative resection, and 74 underwent non-curative resection. RESULTS: The frequency of broad metastases was lower in the curative resection group (8.2%) than in the non-curative resection group (43.2%, p < 0.001). Among all patients, 5-year overall survival rate was higher in the curative resection group (43.0%) than in the non-curative resection group (7.3%, p = 0.004). Among patients who underwent curative resection, 5-year overall survival rate was significantly higher in the AC group (48.2%) than in the non-AC group (38.1%, p = 0.037). Multivariate analysis of all patients revealed pathological N status and non-curative resection as independent predictors of overall survival. In patients who underwent curative resection, advanced age was an independent predictor of relapse-free survival, and AC was an independent predictor of overall survival. CONCLUSION: This multicenter study of colorectal cancer patients with peritoneal metastases revealed that prognosis was more favorable for curable cases than for non-curable cases. Prognosis was more favorable in the AC group than in the non-AC group after curative resection.

Colon inflammatory index as a useful prognostic marker after R0 resection in patients with colorectal cancer liver metastasis.

BACKGROUND: Although R0 resection for colorectal cancer liver metastasis (CRLM) is a promising treatment with improved prognosis, the recurrence rate is still high. No prognostic markers have been reported after resection of CRLM. In this study, we investigated the association between inflammation-based score and prognosis after R0 resection in patients with CRLM. METHODS: We retrospectively investigated 90 patients who underwent R0 resection for CRLM between 2008 and 2018. We calculated colon inflammatory index (CII) (CII0, low risk; CII1, intermediate risk; and CII2, high risk), modified Glasgow prognostic score, prognostic nutritional index, and CRP-to-albumin ratio; and retrospectively assessed the relationship between these scores, the clinicopathological features, and prognosis. RESULTS: The median follow-up period was 44 months (range, 2-101 months). Five-year relapse-free survival (RFS) (CII2; 12.5%, CII1; 14.5%, CII0; 42.9%) and 5-year overall survival (OS) (CII2; 32.4%, CII1; 25.4%, CII0; 57.7%) were significantly lower in the high CII groups (CII1-2) compared with the low CII group (CII0) (p = 0.021 and p = 0.006, respectively). CEA level was significantly higher in the high CII group than the low CII group (12.4 vs 7.3, p = 0.004). Multivariate analysis showed CII score as an independent predictor of RFS (hazard ratio 2.128, 95%CI 1.147-3.430, p = 0.015) and OS (hazard ratio 2.639, 95%CI 1.331-5.323, p = 0.005). CONCLUSION: CII shows promise as a prognostic marker after R0 liver resection in patients with CRLM.

Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation.

BACKGROUND: Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model. METHODS: Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses. RESULTS: Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model. CONCLUSIONS: Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.

Efficacy of risk-stratified indicators for adjuvant chemotherapy with fluorouracil and oxaliplatin after hepatectomy for colorectal cancer liver metastasis.

BACKGROUND: The recurrence rate after hepatectomy for colorectal cancer liver metastasis (CRLM) is high, and there is no consensus regarding the effect of adjuvant chemotherapy (AC) using oxaliplatin (doublet AC) in these patients. METHODS: The present study included 91 patients who underwent hepatectomy for complete resection at our hospitals between 2008 and 2018. Based on whether or not they had undergone doublet AC, patients were divided into AC (n = 35) and non-AC (n = 56) groups. The recurrent risk was evaluated by the Memorial Sloan Kettering Cancer Center clinical risk score (MSKCC-CRS). RESULTS: The number of females and median age were higher in the AC group (51.4% vs 25.0%, p = 0.010 and 67 vs 61 years, p = 0.012, respectively). The median follow-up period was 45 months (range, 6-101 months). Doublet AC was an independent prognostic factor for 5-year relapse-free survival (hazard ratio, 0.225; 95%CI, 0.097-0.522; p < 0.001) and for 5-year overall survival (hazard ratio, 0.165; 95%CI, 0.057-0.476; p < 0.001) in multivariate analysis. In patients with a high risk of recurrence (MSKCC-CRS 3-5), 5-year relapse-free survival and 5-year overall survival was higher in the doublet AC group than in the non-AC group (p < 0.01). In low-risk patients (MSKCC-CRS 0-2), 5-year relapse-free survival and 5-year overall survival were similar between the groups. CONCLUSIONS: Doublet AC could have a positive effect on prognosis after curative resection of CRLM, especially in high-risk patients. The selection of patients and AC regimen should take into consideration the risk of recurrence.

Usefulness of structured-cadaveric training for trans-anal pelvic exenteration.

PURPOSE: Structured training using cadaveric simulation is useful for trans-anal surgery; however, no studies have examined the effectiveness of cadaveric training for advanced trans-anal surgery including pelvic exenteration (PE). METHODS: Twelve colorectal surgeons attended a total of 10 cadaveric simulation training courses between 2016 and 2021 and completed a questionnaire at the end of the program. We divided 14 consecutive patients who underwent trans-anal PE between 2015 and 2021 into two groups: pre-training group and post-training group, and compared the clinico-pathological features between the groups. RESULTS: The median length of clinical experience of the surgeons was 12 years. There was high score agreement among the surgeons that the course was useful for recognition of anatomical and layer structure, training for trans-anal total mesorectal excision and trans-anal PE, and reducing complications specific to the trans-anal approach. Compared with the pre-training group, patients in the post-training group had a higher rate of two-team surgery (77.8% vs 0%, P = .021), and shorter time to specimen removal (273 vs 423 min, P = .045). CONCLUSIONS: Structured-cadaveric training has potential use as a technical step-up in advanced trans-anal surgery that might contribute to better short-term outcomes in the clinical setting.

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability.

Pembrolizumab is a novel immune-checkpoint inhibitor used for treatment of microsatellite instability-high (MSI-H) colorectal cancer. Several studies have reported clinical complete response (CR) after treatment with pembrolizumab, but none has confirmed pathological CR. Here we provide the first description of pathological CR with R0 resection after immune-checkpoint therapy. A 45-year-old man presented at our hospital with abdominal distention and highly elevated tumor markers. Contrast-enhanced abdominal CT showed a 110 × 75 mm bulky mass with markedly swollen lymph nodes and an isolated peritoneal metastasis in the pelvic space. Biopsy revealed poorly differentiated adenocarcinoma. We diagnosed ascending colon cancer cT4aN2bM1c Stage IVc. A biopsy specimen obtained during systemic chemotherapy (FOLFOXIRI) was confirmed pathologically as MSI-H, after which the treatment was changed to pembrolizumab. The tumor markers rapidly decreased to within normal ranges after three courses of treatment. After twenty courses, CT revealed shrinkage of the main tumor, lymph node metastases, and the peritoneal metastasis, and we performed extended right hemi-colectomy with dissection of the peritoneal metastasis. No residual tumor cells were found histologically. The patient achieved pathological CR and the postoperative course was uneventful. An accurate diagnosis and appropriate follow up are crucial for obtaining sufficient therapeutic effect of pembrolizumab.

Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells.

With the emergence of coronavirus disease-2019, researchers have gained interest in the therapeutic efficacy of mesenchymal stem/stromal cells (MSCs) in acute respiratory distress syndrome; however, the mechanisms of the therapeutic effects of MSCs are unclear. We have previously reported that adipose-derived MSCs (AD-MSCs) strengthen the barrier function of the pulmonary vessels in scaffold-based bioengineered rat lungs. In this study, we evaluated whether AD-MSCs could enhance the intercellular barrier function of lung epithelial cells in vitro using a transwell coculture system. Transepithelial electrical resistance (TEER) measurements revealed that the peak TEER value was significantly higher in the AD-MSC coculture group than in the AD-MSC non-coculture group. Similarly, the permeability coefficient was significantly decreased in the AD-MSC coculture group compared to that in the AD-MSC non-coculture group. Immunostaining of insert membranes showed that zonula occuldens-1 expression was significantly high at cell junctions in the AD-MSC coculture group. Moreover, cell junction-related gene profiling showed that the expression of some claudin genes, including claudin-4, was upregulated in the AD-MSC coculture group. Taken together, these results showed that AD-MSCs enhanced the barrier function between lung epithelial cells, suggesting that both direct adhesion and indirect paracrine effects strengthened the barrier function of lung alveolar epithelium in vitro.

Complete closure of a colo-duodenal fistula in a patient with advanced ascending colon cancer after pembrolizumab combined with radiation therapy: a case report.

BACKGROUND: A colo-duodenal fistula is a very rare complication of colon cancer that presents with not only severe clinical symptoms, but a poor prognosis due to locally advanced cancer. A novel immune checkpoint inhibitor for colon cancer patients provides a high objective response rate. Recently, radiation therapy combined with immune checkpoint inhibitor therapy has been reported to have a synergistic antitumor effect. A case of complete closure of a colo-duodenal fistula in a patient with locally advanced colon cancer after combined pembrolizumab and radiation therapy is reported. CASE PRESENTATION: A 66-year-old man presented with abdominal distention. Abdominal contrast-enhanced computed tomography (CT) showed a 80-mm bulky mass in the right upper quadrant. The tumor created a fistula to the second portion of the duodenum. Upper gastrointestinal endoscopy showed a colo-duodenal fistula. Gastro-jejunal bypass and ileostomy were performed to prevent bowel obstruction, followed by systemic chemotherapy. MSI-high was diagnosed on examination of the biopsy specimen. Treatment was then changed to immunotherapy using pembrolizumab; after six courses, the tumor markers were decreased to within normal ranges, but the main tumor increased. Radiation therapy was then given for local control of the main tumor, after which CT showed that all of the tumor, including the main tumor, lymph node metastases, and the colo-duodenal fistula, had gradually shrunk. Follow-up upper gastrointestinal endoscopy showed that the colo-duodenal fistula had closed completely. PET-CT showed no abnormal uptake in all tumors, and clinical complete response was diagnosed. Now, 21 months after diagnosis, the tumor is well controlled without evidence of regrowth. CONCLUSIONS: Pembrolizumab combined with radiation therapy has a potentially dramatic therapeutic effect for advanced colon cancer.

Relationship between hepatic venous anatomy and hepatic venous blood loss during hepatectomy.

PURPOSE: Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy. METHODS: We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n = 18) were analyzed. The results of IVC partial clamping (PC) were additionally examined. RESULTS: The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p < 0.05). The parameters associated with an increased BLSW (> 13.5 mL/kg) were tumor size (> 4 cm), prothrombin activity (< 87%), CVP (> 7 mmHg), area of suprahepatic IVC (< 360 mm2), IVC-RA gap (> 28 mm), longitudinal angle of IVC (< 160°), and axial angle of the MHV (< 55°). A multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.32, p < 0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. No other statistically significant differences in the surgical records were observed in most cases. CONCLUSION: The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy.

Colorectal cancer in Crohn's disease: a series of 6 cases.

BACKGROUND: Colorectal cancer (CRC) is the most malignant complication in patients with Crohn's disease (CD). We report 6 cases of CD-related CRC treated surgically at our hospital. CASE PRESENTATION: From 2010 to 2016, six CD patients were diagnosed with CRC. All patients were diagnosed with CD at < 25 years old, and the interval from onset of CD to diagnosis of CRC was > 10 years (range, 15-42 years) in all patients. The histological type of cancer was mucinous carcinoma in two cases, well-differentiated tubular adenocarcinoma in two cases, and moderately differentiated tubular adenocarcinoma in two cases. CRC was detected by screening colonoscopy in three cases (50%), and from clinical symptoms in the remaining three cases (50%). Two cases underwent colonoscopy within 2 months after symptom onset, detecting CRC in the relatively early stage. However, one case was diagnosed with advanced-stage CRC by endoscopy 1 year after symptom onset, and experienced poor prognosis. CONCLUSIONS: Regular surveillance colonoscopy is needed to detect early-stage CRC in CD patients. Clear surveillance methods need to be established based on evidence.