RESUMEN
Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.
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Camptotecina/análogos & derivados , Neoplasias Colorrectales , Inhibidores de Topoisomerasa I , Humanos , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , Neoplasias Colorrectales/terapia , Citosol , Microambiente TumoralRESUMEN
BACKGROUND: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND. METHODS: We performed a systemic literature review of PubMed, Embase, and Web of Science databases. Perioperative parameters were extracted and pooled for analysis. This meta-analysis provided an analysis of heterogeneity and prediction intervals. RESULTS: Five studies were included: 567 patients divided between 266 robotic and 301 LPLND. Overall operation time was longer in the robotic group than laparoscopic group (difference in means = 67.11, 95% CI [30.80, 103.42], p < 0.001) but the difference in the pelvic lateral lymph dissection time was not statistically significant (difference in means = - 1.212, 95% CI [ - 11.594, 9.171], p = 0.819). There were fewer overall complications in the robotic than in the laparoscopic group (OR = 1.589, 95% CI [1.009, 2.503], p = 0.046), especially with respect to urinary retention (OR = 2.23, 95% CI [1.277, 3.894], p = 0.005). More pelvic lateral lymph nodes were harvested by robotic surgery than by laparoscopy (differences in means = - 1.992, 95% CI [ - 2.421, 1.563], p < 0.001). CONCLUSIONS: In this meta-analysis, robotic pelvic lateral lymph node dissection was associated with more pelvic lateral lymph nodes harvested and lower overall complications, especially urinary retention when compared to LPLND. Further studies are needed to reinforce these findings.
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Laparoscopía , Escisión del Ganglio Linfático , Pelvis , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Escisión del Ganglio Linfático/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
OBJECTIVE: This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC). METHODS: This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals. Secondary outcomes were total and subdomain scores on the Functional Assessment of Cancer Therapy-General (FACT-G), and scores on the FACT/GOG-Ntx subscale and the Brief Pain Inventory-Short Form (BPI-SF), at baseline, weeks 12, 36, and follow-up (week 48). RESULTS: Thirty-two patients met the inclusion criteria and received verum acupuncture (N = 16) or sham acupuncture (N = 16). Under the -intent-to-treat principle, 26 participants were analyzed. Significant changes from baseline for questionnaire scores and sensory NCV were observed in both study groups. Sham acupuncture was associated with significant reductions from baseline in motor NCV and sensory touch thresholds; no such changes were observed with verum acupuncture. No serious adverse events were reported. CONCLUSION: Prophylactic acupuncture may exert neuroprotective effects on mechanical or tactile touch thresholds during chemotherapy regimens in patients with CRC, with evidence of this protectiveness persisting at 6 months' follow-up. The lack of change in motor NCV values with verum acupuncture indicates neuroprotective effects. Sensory NCV values and patient-reported outcomes did not differ significantly between the study groups.
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Terapia por Acupuntura , Antineoplásicos , Fármacos Neuroprotectores , Enfermedades del Sistema Nervioso Periférico , Humanos , Método Simple Ciego , Fármacos Neuroprotectores/efectos adversos , Terapia por Acupuntura/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Antineoplásicos/efectos adversosRESUMEN
The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45+ and CD8+ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.
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Adenocarcinoma , Neoplasias del Colon , Neoplasias Pulmonares , Humanos , Adenocarcinoma/patología , Neoplasias del Colon/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Oxaliplatino/uso terapéutico , Células Dendríticas/metabolismoRESUMEN
Ability of IL-17-producing CD8+ T cells (Tc17) to transform into cytotoxic anti-tumour effectors makes them a promising candidate for immune effector cell (IEC) therapy. However, key factors regulating Tc17 reprogramming remain poorly defined, hindering translation of Tc17-based IEC use from bench to bedside. We probed the effects of multiple cytokines and underlying signalling pathways on Tc17 cells and identified pivotal role for IL-4 and PI3K/AKT in promoting Tc17 transformation into cytotoxic IFN-γ-producing IECs, an effect dependent on Eomes expression. IL-4 not only triggered Tc17 cytotoxicity, but also induced cell expansion, which significantly improved the antitumour potential of Tc17 cells compared to that of IFN-γ-producing CD8+ T cells (Tc1) in a murine model. Furthermore, IL-4/AKT signalling drove the upregulation of the T-cell receptor-associated transmembrane adaptor 1 (Trat1) in Tc17 cells to promote IL-4-induced T-cell receptor stabilization and Tc17 cytotoxicity. Finally, we proposed a possible procedure to expand human Tc17 from peripheral blood of cancer patients, and confirmed the function of IL-4 in Tc17 reprogramming. Collectively, these results document a novel IL-4/AKT/Eomes/Trat1 axis that promotes expansion and transformation of Tc17 cells into cytotoxic effectors with a therapeutic potential. IL-4 priming of Tc17 cells should be further explored as a cell therapy engineering strategy to generate IECs to augment anti-tumour responses.
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Linfocitos T CD8-positivos , Interleucina-4 , Traslado Adoptivo , Animales , Humanos , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Ratones , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
BACKGROUND: Peritoneal contamination is a major concern during natural orifice specimen extraction after laparoscopic colorectal resection (LCR-NOSE), but few data are available. We explored the prevalence, risk factors, and association between clinical outcomes and infectious complications in patients with positive peritoneal drain fluid culture (PDFC) after LCR-NOSE. METHOD: We retrospectively analyzed patient records in our prospectively maintained registry database who underwent LCR-NOSE between 2011and 2020. Peritoneal drain fluid was collected within 12 h post-operative and cultures for microorganisms were obtained. The relationships between PDFC, clinical variables, and infectious complications were examined by univariate and multivariable analysis. RESULTS: Of 241 consecutive patients who underwent LCR-NOSE and drainage fluid culture, 59 (24.5%) had PDFC. Anterior resection (Odds ratio OR 2.40) was identified as an independent predictor for PDFC. Twenty-eight patients (11.6%) developed infectious complications. Multivariable analysis identified low anterior resection (OR 2.74), prolonged operative time (OR 3.20), and PDFC (OR 5.14) as independent risk factors. Pseudomonas aeruginosa was the most frequently found microorganism (OR 5.19) responsible for infectious complications. CONCLUSIONS: Microorganisms are commonly present in the peritoneum after LCR-NOSE and play a critical role in the development of infectious complications and related morbidity. Specific caution is warranted in patients contaminated with specific types of microorganisms.
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Cirugía Colorrectal , Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Humanos , Peritoneo , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Estudios Retrospectivos , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Although reduced port laparoscopic surgery (RPLS), defined as laparoscopic surgery performed with the minimum possible number of ports and/or small-sized ports, is less invasive than conventional laparoscopic surgery by reducing the number of surgical wounds, an extension of the incision is still needed for specimen extraction, which can undermine the merits of RPLS. OBJECTIVE: To determine the impact of natural orifice specimen extraction (NOSE) in patients undergoing RPLS for colorectal cancer. The endpoints were perioperative outcome and oncologic safety at 3 years. SETTING: Single-center experience (2013-2019). PATIENTS: We retrospectively analyzed our prospectively collected patient records (American Joint Committee on Cancer (AJCC) stage I-III sigmoid or upper rectal cancer (tumor diameter ≤ 5 cm) who underwent curative anterior resection via RPLS. We excluded patients who did not undergo intestinal anastomosis. INTERVENTIONS: Perioperative and oncologic outcomes were compared between patients undergoing natural orifice (RPLS-NOSE) or conventional (mini-laparotomy) specimen extraction (RPLS-CSE). Patients were matched by propensity scores 1:1 for tumor diameter, AJCC stage, American Society of Anesthesiologists score and tumor location. RESULTS: Of 119 eligible patients, 104 were matched (52 RPLS-NOSE; 52 RPLS-CSE) by propensity scores. Compared with RPLS-CSE, RPLS-NOSE was associated with longer operative time (223.9 vs. 188.7 min; p = 0.003), decreased use of analgesics (morphine dose 33.9 vs. 43.4 mg; p = 0.011) and duration of hospital stay (4.2 vs. 5.1 days; p = 0.001). No statistically significant difference was found in morbidity or wound-related complication rates between the two groups. After a median follow-up of 34.3 months, no local recurrence was observed in RPLS-NOSE. The 3-year disease-free survival did not differ statistically significantly between groups (90.9 vs. 90.5%; p = 0.610). CONCLUSION: NOSE enhances the advantages of RPLS by avoiding the need for abdominal wall specimen extraction in patients with tumor diameter ≤ 5 cm. Surgical and oncologic safety are comparable to RPLS with CSE.
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Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Neoplasias del Recto , Humanos , Laparotomía , Puntaje de Propensión , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Cytoreductive surgery (CRS) for colorectal cancer peritoneal carcinomatosis has been shown to prolong survival with acceptable morbidity rates. Total pelvic peritonectomy (TPP), or complete removal of all pelvic peritoneum, constitutes an important and technically challenging component of CRS. Here we report our experience and describe our technique of laparoscopic total pelvic peritonectomy (LTPP), using a photographic/videographic step-by-step guide. METHODS: All patients who underwent LTPP for pelvic carcinomatosis from a colorectal origin were included in the study. Only patients with peritoneal cancer index (PCI) score of ≤ 10 were selected for CRS with LTPP. Patients who had extra-abdominopelvic cavity metastases were excluded. The final decision to proceed with CRS was made following laparoscopic assessment. RESULTS: From January 2017 to December 2020, 15 consecutive patients underwent LTPP for colorectal cancer pelvic carcinomatosis. Median patient age and PCI score was 53 years (range 33-78) and 8 (range 3-10), respectively. Complete cytoreduction was achieved in all patients. Thirteen patients (87%) underwent concomitant hyperthermic intraperitoneal chemotherapy (HIPEC). The median operative duration was 748 min (interquartile range [IQR] 681-850). Median intra-operative blood loss and length of hospital stay was 100 ml (IQR 50-300) and 10 days (IQR 8-12), respectively. Five patients (33%) experienced 30-day post-operative morbidity, with one (6.7%) experiencing a higher grade (Clavien-Dindo IIIa) complication. Median follow-up duration was 13 months (IQR 3-19), during which four (27%) had systemic recurrence and one (6.7%) died after 15 months following peritoneal and systemic recurrences. CONCLUSION: LTPP is a feasible option for low-volume pelvic carcinomatosis from colorectal cancer, offering the benefits of a minimally invasive approach. Strict patient selection is essential, and the procedure should be converted if the PCI score cannot be assessed or complete cytoreduction cannot be achieved. Proficiency at laparoscopic pelvic surgery is mandatory for performing LTPP.
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Neoplasias Colorrectales , Hipertermia Inducida , Laparoscopía , Neoplasias Peritoneales , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Persona de Mediana Edad , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: There is still no consensus on the management of intraperitoneal anastomotic leakage after colonic surgery. Among of various treatment strategies, laparoscopic redo anastomosis for intraperitoneal leakage has rarely been reported in the literature and is condemned by some. The aim of this study is to demonstrate the feasibility and safety of laparoscopic redo anastomosis for intraperitoneal anastomotic leakage. METHODS: Retrospective chart review of laparoscopic redo anastomosis for intraperitoneal anastomotic leakage after colonic surgery from January 2013 to May 2020. An accompanying video demonstrates the technique. RESULTS: Fifteen consecutive patients underwent laparoscopic redo anastomosis for management of leakage after colonic surgery; two patients required conversion to open repair. A protective stoma was created in three patients during the second operation. There was no re-leakage nor mortality in this series. CONCLUSIONS: Laparoscopic redo anastomosis was feasible and safe for the management of intraperitoneal anastomotic leakage after colonic surgery. Considering the advantages of re-do laparoscopy, this procedure should be part of every surgeon's armamentarium to deal with anastomotic leakage and represents a logical alternative to the "Diversion and Drainage" technique.
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Fuga Anastomótica , Laparoscopía , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/cirugía , Humanos , Laparoscopía/métodos , Reoperación/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: There is still no consensus on the management of colorectal anastomotic leakage after low anterior resection. The goal was to evaluate the outcomes of patients who underwent transanal endoluminal repair + laparoscopic drainage ± stoma vs. drainage only ± stoma. METHODS: Retrospective chart review of patients sustaining anastomotic leakage after laparoscopic low anterior resection between January 2013 and September 2020 who required laparoscopic reoperation. RESULTS: Forty-nine patients were included, 22 patients underwent combined laparoscopy and transanal endoluminal repair and 27 patients had drainage with a stoma (n = 16) or drainage alone (n = 11), without direct anastomotic repair. The overall morbidity rate was 30.6% and the mortality rate was 2%. Combined laparoscopic lavage/drainage and transanal endoluminal repair of anastomotic leakage was associated with a lower complication rate (13.6% vs. 44.4%, p = 0.03) and fewer intraabdominal infections (4.5% vs. 29.6%, p = 0.03) compared with no repair. CONCLUSIONS: Combined laparoscopic lavage/drainage and transanal endoluminal repair is effective in the management of colorectal anastomosis leakage and was associated with lower morbidity-in particular intraabdominal infection-compared with no repair. However, our results need to be confirmed in larger, and ideally randomized, studies.
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Anastomosis Quirúrgica , Fuga Anastomótica , Proctectomía , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Angioplastia , Humanos , Laparoscopía , Proctectomía/efectos adversos , Estudios RetrospectivosRESUMEN
INTRODUCTION: No universal consensus exists on the management of intraperitoneal anastomosis leakage after colonic surgery. The aim of the study was to evaluate the outcomes of laparoscopic reintervention without stoma creation for intraperitoneal leaks after colonic surgery. MATERIAL AND METHODS: Single tertiary center study conducted from January 2010 to December 2020. 54 patients with intraperitoneal leakage were divided into 2 groups according to whether they received a stoma (n = 37) or not (n = 17) during laparoscopic reintervention. Short term outcome was analyzed. RESULTS: Patients in the no stoma group had lower American Society of Anesthesiologists (ASA) score (P = .009), lower Acute Physiology And Chronic Health Evaluation II (APACHE II) score (5 vs. 10; P < .001) compared with the stoma group. Intensive care unit admission (43.2% vs. 5.8%; P = .006) and major complications (35.1% vs. 5.8%; P = .015) occurred more in the stoma group compared to the no stoma group. After multivariate logistic regression analysis, initial surgical procedure (P = .001) and APACHE II score (P = .039) were significant predictors of no stoma. The APACHE II score(P = .035) was an independent predictor of major complications. Finally, Receiver Operating Characteristic curve analysis showed that the cutoff value of APACHE II score for no stoma was 7.5. CONCLUSIONS: In our study, APACHE II score was an independent predictor of stoma formation and the cutoff value of APACHE II score for no stoma was 7.5. Our results need to be confirmed by larger and randomized studies. In particular, a specific APACHE II threshold to omit a stoma in this setting remains to be determined.
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Laparoscopía , Estomas Quirúrgicos , Humanos , Fuga Anastomótica/cirugía , Fuga Anastomótica/etiología , Colon/cirugía , Laparoscopía/efectos adversos , Pronóstico , Estudios Retrospectivos , Curva ROC , Estomas Quirúrgicos/efectos adversosRESUMEN
AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.
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ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Estrés del Retículo Endoplásmico , Proteínas de Choque Térmico/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Anciano , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Femenino , Homeostasis/efectos de los fármacos , Humanos , Muerte Celular Inmunogénica/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Ratones Endogámicos BALB C , Modelos Biológicos , Análisis Multivariante , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Unión Proteica/efectos de los fármacos , Estabilidad Proteica/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
Immunosurveillance and immunoscavenging prompted by preoperative chemoradiotherapy (CCRT) may contribute to improve local control and increase survival outcomes for patients with locally advanced rectal cancer (LARC). In this study, we investigated several genotypes of pattern recognition receptors (PRRs) and their impact on therapeutic efficacy in LARC patients treated with CCRT. We found that homozygosis of formyl peptide receptor 1 (FPR1) (E346A/rs867228) was associated with reduced 5-year overall survival (OS) by Kaplan-Meier analysis (62% vs. 81%, p = 0.014) and multivariate analysis [hazard ratio (HR) = 3.383, 95% CI = 1.374-10.239, p = 0.007]. Moreover, in an animal model, we discovered that the FPR1 antagonist, Boc-MLF (Boc-1), reduced CCRT therapeutic efficacy and decreased cytotoxic T cells and T effector memory cells after chemoradiotherapy treatment. Pharmacologic inhibition of FPR1 by Boc-1 decreased T lymphocyte migration to irradiated tumor cells. Therefore, these results revealed that the FPR1 genotype participates in CCRT-elicited anticancer immunity by reducing T lymphocytes migration and infiltration, and that the FPR1-E346A CC genotype can be considered an independent biomarker for chemo- and radiotherapy outcomes.
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Receptores de Formil Péptido/metabolismo , Animales , Quimioradioterapia , Femenino , Humanos , Ratones , Terapia Neoadyuvante , Pronóstico , Neoplasias del RectoRESUMEN
INTRODUCTION: Natural orifice specimen extraction is the next step in minimally invasive colorectal surgery but can be technically challenging, with additional risks, especially for oncologic surgery. For several key reasons, sigmoid volvulus is well suited for natural orifice specimen extraction surgery. We describe our method and experience with double-stapled anastomosis transrectal natural orifice specimen extraction for sigmoid volvulus. TECHNIQUE: Using 3- or 4-port laparoscopy, the mesentery is separated from the long sigmoid loop. After the distal bowel is tied off and washed out, the rectum is completely transected and the proximal bowel delivered transrectally through a wound protector. Proximal transection is performed externally, and the circular stapler anvil is set before the bowel is returned into the abdominal cavity. The rectum stump is closed with an endoscopic linear stapler, and a circular-stapled anastomosis is performed. RESULTS: After successful endoscopic decompression, 6 patients underwent elective laparoscopic sigmoidectomy with natural orifice specimen extraction for volvulus at China Medical University Hospital from 2015 to 2020. The median operative time was 179 minutes (range, 151-236 min). No intraoperative complications were encountered. The median postoperative length of stay was 4 days (range, 2-9 d). One patient experienced postoperative small-bowel ileus resulting in readmission. The median follow-up duration was 12 months (range, 2-49 mo). One recurrence of volvulus was recorded 27 months postsurgery. CONCLUSION: Uncomplicated sigmoid volvulus can be treated effectively with sigmoidectomy and natural orifice specimen extraction. Surgeons who attempt this procedure should be well versed with conventional laparoscopy but do not necessarily need to be experienced with natural orifice specimen extraction for successful surgery.
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Colectomía/métodos , Colon Sigmoide/cirugía , Vólvulo Intestinal/cirugía , Laparoscopía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Descompresión Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sigmoidoscopía , Manejo de Especímenes/métodos , Cirugía Endoscópica Transanal/métodos , Adulto JovenRESUMEN
AIM: Anastomotic stricture following anterior resection is an uncommon but challenging problem. Endoscopic dilatation and transanal endoscopic surgery (TES) are proven methods of treatment. However, a small proportion of patients repeatedly fail transanal local therapy for underlying reasons of tension, insufficient blood supply or irradiated tissue, eventually necessitating a complete anastomotic excision. We aimed to combine transanal minimally invasive surgery (TAMIS) with an abdominal approach in redo anastomoses for severe refractory anastomotic strictures. METHOD: For the TAMIS phase, we use a Lonestar® retractor with a GelPOINT® Path transanal access platform. A circumferential full thickness rectotomy is performed and the dissection is continued proximally in the mesorectal fascial plane past the strictured segment to meet the abdominal dissection or until the peritoneal cavity is entered, facilitating mobilization of the rectum. The abdominal phase is performed as usual with sufficient mobilization of the left colon to enable tension-free redo anastomosis. An accompanying video demonstrates this technique. RESULTS: Two patients with refractory anastomotic strictures following a previous low anterior resection underwent the procedure. One patient had laparoscopy followed by TAMIS and the other had TAMIS followed by laparotomy. Both cases were performed by surgeons experienced in laparoscopy and TES. One patient had postoperative ileus which resolved conservatively. Both anastomoses were widely patent on follow-up. CONCLUSION: TAMIS combined with a conventional abdominal approach offers significant technical advantages over a totally abdominal approach for the definitive management of patients with severe anastomotic strictures refractory to first-line methods of therapy. The operator should already be proficient with TES.
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Proctectomía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Abdomen , Constricción Patológica/etiología , Constricción Patológica/cirugía , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Recto/cirugíaRESUMEN
AIM: Following extended left-sided colorectal resection, creation of the anastomosis can be challenging due to insufficient length of the remaining proximal and distal bowel. Retroileal pull-through and the Deloyers procedure are feasible but require ligation of the middle colic vessels and additional right colonic mobilization. The aim of this study was to describe our initial experience with an alternative technique for performing tension-free anastomosis following minimally invasive left-sided resection. METHOD: This was a retrospective case series of all patients who underwent a retrojejunal trans-mesenteric pull-through following elective laparoscopic left-sided colorectal surgery between September 2019 and September 2020. Placing the retrojejunal window 15-20 cm distal to the duodenojejunal junction allows the transverse colon to pass via the most direct route through the base of the proximal jejunal mesentery to the distal colon or rectal stump instead of passing over the small bowel, yielding additional length for the anastomosis. An accompanying video demonstrates this technique for three different case scenarios. RESULTS: Seven consecutive patients underwent this approach following colorectal resection; three had inherently shorter left colons, two had synchronous left-sided tumours and two had inadvertent intraoperative marginal artery injury. There were no anastomotic complications or early postoperative morbidity related to the mesenteric window. The additional time taken for the procedure ranged from 5 to 35 min. The risk of complications related to extended left-sided resections may possibly be reduced, although further studies are required to evaluate this. CONCLUSION: Retrojejunal trans-mesenteric pull-through is a novel, but straightforward, safe and useful option for reducing tension in laparoscopic left-sided colorectal anastomoses.
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Neoplasias Colorrectales , Laparoscopía , Anastomosis Quirúrgica , Colectomía , Neoplasias Colorrectales/cirugía , Humanos , Mesenterio , Estudios RetrospectivosRESUMEN
BACKGROUND: Although the short-term advantages of natural orifice specimen extraction are widely recognized, controversy exists concerning oncologic safety after laparoscopic surgery for colorectal cancer. OBJECTIVE: This study aimed to investigate the impact of natural orifice specimen extraction on local recurrence and long-term survival of patients undergoing colorectal cancer surgery. DESIGN: This is a propensity score-matched comparative study. SETTING: This study presents a single-center experience. PATIENTS: We retrospectively analyzed the records of patients who underwent curative laparoscopic anterior resection for American Joint Committee on Cancer stage I to III sigmoid or upper rectal cancer in 2011 to 2014, based on prospectively collected data. INTERVENTIONS: Oncologic outcomes were compared between patients undergoing natural orifice or conventional specimen extraction by minilaparotomy. Patients were matched 1:1 according to propensity scores calculated by logistic regression analysis with the following covariates: American Joint Committee on Cancer stage, tumor diameter, age, sex, BMI, and T stage. Cox proportional hazards regression analysis was performed to determine the impact on oncologic outcome. MAIN OUTCOME MEASURES: The primary outcomes measured were local recurrence and disease-free survival rates at 5 years. RESULTS: Of 392 eligible patients, 188 were matched (94 undergoing natural orifice specimen extraction and 94 undergoing conventional extraction by minilaparotomy). Median follow-up was 50.3 months. The cumulative local recurrence risk at 5 years was 2.3% and 3.5% (p = 0.632), whereas 5-year disease-free survival for all tumor stages combined was 87.3% and 82.0% (p = 0.383) in laparoscopic anterior resection with natural orifice specimen extraction and conventional extraction groups. T3 and T4 stages were the only variables independently associated with disease-free survival. LIMITATIONS: This study was limited because it focused on a single center, was a retrospective analysis, contained no long-term anorectal function testing, and had a small sample size. CONCLUSION: Long-term oncologic outcomes of patients undergoing laparoscopic anterior resection with natural orifice specimen extraction for sigmoid and upper rectal cancer do not differ from those undergoing conventional extraction. Thus, natural orifice specimen extraction could be a viable alternative to reduce abdominal wall insult in laparoscopic colorectal operations for malignancy in selected patients. See Video Abstract at http://links.lww.com/DCR/B241. RESULTADOS ONCOLÓGICOS A LARGO PLAZO DE RESECCIONES ANTERIORES LAPAROSCÓPICAS PARA CÁNCER A TRAVÉS DE ORIFICIO NATURAL FRENTE A EXTRACCIÓN CONVENCIONAL DEL ESPÉCIMEN: UN ESTUDIO DE CASOS Y CONTROLES: Si bien las ventajas a corto plazo de la extracción de especímenes por orificio natural son ampliamente reconocidas, existe controversia con respecto a la seguridad oncológica después de la cirugía laparoscópica para el cáncer colorrectal.Investigar el impacto de la extracción de especímenes por orificio natural en la recurrencia local y la supervivencia a largo plazo de pacientes sometidos a cirugía de cáncer colorrectal.Estudio comparativo con emparejamiento por puntuación de propensión.Experiencia en un centro único.Analizamos retrospectivamente los registros de pacientes que se sometieron a resección anterior laparoscópica curativa para cáncer sigmoideo o rectal superior AJCC en estadio I-III en 2011-2014, con base en datos recolectados prospectivamente.Los resultados oncológicos se compararon entre pacientes sometidos a extracción por orificio natural o convencional mediante minilaparotomía de especímenes. Los pacientes fueron emparejados 1:1 de acuerdo con los puntajes de propensión calculados por análisis de regresión logística con las siguientes covariables: estadio AJCC, diámetro del tumor, edad, sexo, índice de masa corporal y estadio T. Se realizó un análisis de regresión de riesgos proporcionales de Cox para determinar el impacto en el resultado oncológico.Recurrencia local y tasas de supervivencia libre de enfermedad a los 5 años.De 392 pacientes elegibles, 188 fueron emparejados (94 sometidos a extracción de espécimen por orificio natural y 94 a extracción convencional por minilaparotomía). La mediana de seguimiento fue de 50.3 meses. El riesgo cumulativo de recurrencia local a 5 años fue de 2.3% y 3.5% (p = 0.632), mientras que la supervivencia libre de enfermedad a 5 años para todas las etapas tumorales combinadas fue de 87.3% y 82.0% (p = 0.383) en los grupos de resección anterior laparoscópica con extracción de espécimen por orificio natural y extracción convencional, respectivamente. Las etapas T3 y T4 fueron las únicas variables asociadas independientemente con la supervivencia libre de enfermedad.Centro único, análisis retrospectivo, ausencia de pruebas de función anorrectal a largo plazo y tamaño de muestra pequeño.Los resultados oncológicos a largo plazo de los pacientes sometidos a resección anterior laparoscópica con extracción de espécimen por orificio natural para cáncer sigmoideo y rectal superior no difieren de los de aquellos sometidos a extracción convencional. Por lo tanto, la extracción de especímenes por orificio natural podría ser una alternativa viable para reducir el insulto a la pared abdominal en operaciones colorrectales laparoscópicas por malignidad en pacientes selectos. Consulte Video Resumen en http://links.lww.com/DCR/B241.
Asunto(s)
Neoplasias Colorrectales/cirugía , Laparoscopía/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Recurrencia Local de Neoplasia/epidemiología , Anciano , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/tendencias , Masculino , Persona de Mediana Edad , Cirugía Endoscópica por Orificios Naturales/métodos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Evaluación de Resultado en la Atención de Salud , Puntaje de Propensión , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Neoplasias del Colon Sigmoide/cirugíaRESUMEN
The expression of programmed cell death 1 ligand 1 (PD-L1) and interferon-γ (IFN-γ) is of great interest for the development of chemoradiotherapy and immune checkpoint inhibitor treatments. Patients with nodal metastasis (pN+) tend to have a poor prognosis, even after neoadjuvant chemoradiotherapy (neoCRT) and surgical treatment. In this study, we examined the roles of tumor PD-L1 and IFN-γ before and after neoCRT in locally advanced rectal cancer (LARC) patients. Our results demonstrate that patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year disease-free survival (DFS) and overall survival (OS) compared with those with low PD-L1 expression (p < 0.001). Furthermore, in the pN+ population, patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year DFS and OS. PD-L1 and IFN-γ upregulation increased in tumor tissues after neoCRT, and patients with high PD-L1 and high IFN-γ exhibit improved 5-year DFS and OS (p = 0.04 and p = 0.001, respectively). To the best of our knowledge, this study is the first to demonstrate that PD-L1 upregulation in a pN+ cohort correlates with improved prognosis, which is similar to that in patients without nodal metastasis. Moreover, this study verified that PD-L1 and IFN-γ were upregulated by neoCRT treatment in LARC patients and demonstrated that neoCRT may be useful not only for immune checkpoint inhibitor treatment but also for reinvigorating preexisting anti-cancer immunity.
Asunto(s)
Antígeno B7-H1/biosíntesis , Neoplasias del Recto/terapia , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico , Neoplasias del Recto/metabolismo , Neoplasias del Recto/patologíaRESUMEN
Rectal cancer, which comprises 30% of all colorectal cancer cases, is one of the most common forms of cancer in the world. Patients with locally advanced rectal cancer (LARC) are often treated with neoadjuvant chemoradiotherapy (neoCRT) followed by surgery. However, after neoCRT treatment, approximately one-third of the patients progress to local recurrence or distant metastasis. In these studies, we found that patients with tumors that exhibited cytosolic HMGB1(Cyto-HMGB1) translocation and/or the presence of PD-1+ tumor-infiltrating lymphocytes (TILs) before treatment had a better clinical outcome. The better outcome is likely due to the release of HMGB1, which triggers the maturation of dendritic cells (DCs) via TLR4 activation, and the subsequent recruitment of PD-1+ tumor-infiltrating lymphocytes to the tumor site, where they participate in immune-scavenging. In conclusion, our results provide evidence that cyto-HMGB1 and/or PD-1+TIL are not only predictive biomarkers before treatment, but they can also potentially designate patients for personalized oncological management including immunotherapy.