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PubMed2005

Sentinel node detection after preoperative short-course radiotherapy in rectal carcinoma is not reliable.

BACKGROUND: Sentinel node (SN) detection may be used in patients with colonic carcinoma. However, its use in patients with rectal carcinoma may be unreliable. To address this, SN detection was evaluated in patients with rectal carcinoma after short-course preoperative radiotherapy. METHODS: Patent Blue V (1-2 ml) was injected peritumorally and submucosally directly after total mesorectal excision (TME) in 34 patients. The first one to four blue lymph nodes were categorized as SNs. All lymph nodes (non-SNs and SNs) were examined by conventional haematoxylin and eosin stained sections. If the SN was negative for metastasis, additional sections were immunostained with anticytokeratin CK7/8. In addition, SN detection was performed in 57 patients with colonic carcinoma. RESULTS: A SN was identified in 26 of 34 patients with rectal carcinoma. In three the SN was the only positive lymph node. There were six false-negative SNs (sensitivity 40 per cent) and two patients were upstaged. By contrast, SN detection was possible in 56 of 57 patient with colonic carcinoma with a sensitivity of 90 per cent, and four patients were upstaged. CONCLUSION: The SN procedure for rectal carcinoma is not reliable in combination with TME and preoperative short-course radiotherapy.

Adult↗

PubMed2007

Impact of radiotherapy on local recurrence of rectal cancer in Norway.

BACKGROUND: The purpose of this study was to analyse the impact of radiotherapy on local recurrence of rectal cancer in Norway after the national implementation of total mesorectal excision (TME). METHODS: This was a prospective national cohort study of 4113 patients undergoing major resection of rectal carcinoma between November 1993 and December 2001. RESULTS: The proportion of patients who had radiotherapy before or after operation increased from 4.6 per cent in 1994 to 23.0 per cent in 2001. The cumulative 5-year local recurrence rate decreased from 16.2 to 10.7 per cent. Multivariable analysis showed that preoperative radiotherapy significantly reduced local recurrence (hazard ratio 0.59 (95 per cent confidence interval 0.39 to 0.87)). The use of preoperative radiotherapy in patients from a local hospital offering radiotherapy was 50 per cent higher than that for patients from a hospital without such services (P = 0.003); cumulative 5-year local recurrence rates for these patients were 10.6 and 15.8 per cent respectively (P < 0.001). CONCLUSION: Following national implementation of TME for rectal cancer, increased use of preoperative radiotherapy appeared to reduce recurrence rates further.

Aged↗

PubMed2026

Oncogenic Mutations and Tumor Microenvironment Alterations in Diffuse Large B-Cell Lymphoma With Bulky Disease.

BACKGROUND: Bulky disease represents a clinically aggressive subset of diffuse large B-cell lymphoma (DLBCL) associated with adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on bulky disease in DLBCL. METHODS: We analyzed a cohort of 939 patients with newly diagnosed DLBCL. Using DNA (n = 934) and RNA (n = 524) sequencing, we compared oncogenic mutations and tumor microenvironment (TME) alterations based on tumor diameter, with cutoff values at 5.0 cm and 10.0 cm. Further stratification by mutations in key genes (CD58, STAT6, EBF1) correlated with tumor diameter revealed distinct transcriptomic and immunologic profiles. Subsequent single-cell RNA sequencing, guided by these mutational signatures, resolved the cellular heterogeneity within the TME. RESULTS: Integrative analysis revealed that tumor diameter correlated with increased incidence of mutations in CD58, STAT6, and EBF1; adverse genetic subtypes such as EZB-like MYC+ and TP53Mut; activation of oncogenic pathways (JAK/STAT, BCR, PI3K, and MYC); and an immunosuppressive tumor microenvironment. Notably, immune checkpoint molecules varied across the bulky stages, with CTLA-4, TIGIT, ICOS, and CD28 expression inversely correlated with tumor diameter, while CD70 and 4-1BBL expression positively correlated. Single-cell RNA sequencing further revealed mutation-specific tumor microenvironment insights. CD58-mutated tumor exhibited a profoundly immune-deserted microenvironment dominated by malignant B cells with minimal immune infiltration, whereas STAT6-mutated tumor was associated with increased fibroblasts and CD4 + T cells, particularly regulatory T cells (Treg) and Th1-like cells; EBF1-mutated tumor was characterized by increased proportions of malignant B cells. CONCLUSIONS: Collectively, our findings highlight the biological complexity of bulky disease, identifying candidate molecular targets and providing a biological framework for future therapeutic hypothesis generation in this clinically aggressive subset of DLBCL.

Humans↗

PubMed2026

Integrated Genomic and Proteomic Analysis Reveals T-B Lymphocyte Signatures in the MYCN Driven "Immune Desert" of Specific Neuroblastoma Subtypes.

AIMS: This study aims to systematically dissect how MYCN amplification shapes the immunosuppressive tumor microenvironment (TME) in high-risk neuroblastoma, elucidating key mechanisms underlying immune evasion. METHODS: We performed an integrated multi-omics analysis of bulk RNA-seq (n = 721), single-cell RNA-seq (n = 9), proteomic data (n = 49) and spatial transcriptomics (Visium, with external validation in melanoma). Analyses included unsupervised clustering, cell-cell communication inference, transcriptional regulatory network reconstruction, and spatial proximity assessment to map the immune landscape. RESULTS: A distinct molecular subtype (Class C), defined by MYCN amplification and poor prognosis, exhibited a comprehensive "immune desert" phenotype characterized by low immune scores and minimal leukocyte infiltration. Single-cell analysis confirmed significant depletion of T and B lymphocytes within the Class C TME. Dysregulated transcriptional networks were identified, including upregulation of REL and EOMES in T cells-with EOMES potentially driving exhaustion via regulation of Transient Receptor Potential (TRP) genes, and REL inhibition enhancing cytotoxic function in vitro. A unique immunosuppressive B-cell subset (B7) engaged in enhanced crosstalk with exhausted T cells and harbored a MYC-centered network linked to cell cycle dysregulation and poor survival. Spatial transcriptomics revealed significant proximity between B7-active regions and Treg/exhaustion-enriched areas, externally validated in melanoma. Proteomic data validated elevated REL expression in MYCN-amplified tumors. CONCLUSION: This work delineates the immunosuppressive architecture of MYCN-driven neuroblastoma, revealing novel regulatory nodes within specific lymphocyte compartments. Integrating single-cell, spatial, and proteomic evidence, we propose REL inhibition as a therapeutic candidate, the EOMES/TRP axis as a bioinformatically supported hypothesis, and the B7/MYC hub as a hypothesis supported by transcriptomic and spatial evidence.

Humans↗

PubMed2006

Surgical outcomes after total mesorectal excision for rectal cancer.

BACKGROUND AND OBJECTIVES: This study reviewed the results of surgery for distal rectal cancer following the introduction of total mesorectal excision (TME) for rectal cancer. METHODS: Two hundred sixty-four patients who had undergone elective curative surgical resection of rectal cancer within 12 cm of the anal verge were included. Comparisons were made between patients who had different surgical procedures. RESULTS: The overall operative mortality rate was nil, and the morbidity 39.4%. With a mean follow-up of 34 months (range 5-105 months), local recurrence occurred in 21 of the patients. The 3- and 5-year actuarial local recurrence rates were 9% and 12%, respectively for the whole group. Abdominoperineal resection (APR) was necessary in 65 of 264 (24.6%) of the patients, with a very low local recurrence rate in this subgroup (5% at 3 years). On multivariate analysis, only stage was a significant prognosticator of overall survival (P = 0.012). CONCLUSIONS: With the practice of TME, APR was still necessary in 25% of patients with rectal cancer within 12 cm of the anal verge. Type of surgery and tumor distance from the anal verge influenced local recurrence rates, but only initial tumor stage was associated with long-term survival.

Adult↗

PubMed2026

Icaritin Sensitizes Hepatocellular Carcinoma to PD-L1 Therapy by NQO1-Dependent Ferroptosis Induction.

Hepatocellular carcinoma (HCC) remains challenging with limited immunotherapy response. Despite its clinical promise in advanced HCC, the mechanisms of icaritin, especially concerning ferroptosis induction and immune modulation, remain elusive. This study aims to determine if the antitumor effect of icaritin involves the induction of ferroptosis via NAD(P)H quinone oxidoreductase 1 (NQO1) and if it can augment the efficacy of programmed cell death 1 ligand 1 (PD-L1) therapy by potentiating natural killer (NK) cell activity. Using human HCC cell lines (Huh7, Hep3B, PLC/PRF/5, SNU-449, and MHCC97-H) and two synergistic mouse models (Hepa1-6 and SgPten/c-Met), we examined icaritin's inhibition of tumor growth and induction of ferroptosis via the NQO1 pathway, monitoring key markers (reactive oxygen species [ROS], glutathione peroxidase 4 [GPX4], ferritin heavy chain 1 [FTH1]). The NQO1 inhibitor dicoumarol was employed to validate the pathway. Tumor microenvironment (TME) remodeling was assessed through cancer-associated fibroblasts (CAFs) markers and immune cell profiling, focusing on NK cell infiltration. Combination therapy with anti-PD-L1 was tested in vivo. Icaritin significantly inhibited HCC growth in vitro and in vivo. Its antitumor effect was mediated by NQO1-mediated ferroptosis, via elevated ROS, diminished mitochondrial membrane potential, and downregulated GPX4 and FTH1. Analysis of The Cancer Genome Atlas (TCGA) data revealed that NQO1 is overexpressed in human HCC tissues. Icaritin enhanced NK cell infiltration while reducing CAF abundance and suppressing recombinant focal adhesion kinase (FAK) and discoidin domain receptor 1 (DDR1) signaling. Notably, icaritin synergized with anti-PD-L1 therapy to enhance tumor suppression without increasing toxicity, correlating with potentiated NK cell immunity. Our findings demonstrate that icaritin triggered NQO1-mediated ferroptosis and remodeled TME to enhance NK cell recruitment and PD-L1 therapy efficacy. This provides rationale for evaluating icaritin-based combination immunotherapy in HCC through dual action on ferroptosis and NK cell activation.

Ferroptosis↗

PubMed2005

Surgical results of total mesorectal excision for rectal cancer in a specialised colorectal unit.

Our aim was to review the results of total mesorectal excision (TME) in a specialised colorectal unit. Perioperative and follow-up data were prospectively collected in a computerised database. A review of all the records was made. The morbidity rate was about 14%, and was higher in patients with coloplasty due to a higher anastomotic leak rate. The local recurrence rate was 2%, the distant metastasis rate was 11%, and both local and distant metastasis occurred in 4%. About 95% of recurrence occurred within 3 years. There was better bowel function in patients with a colonic J-pouch in the first 2 years after surgery, but the advantage disappeared thereafter. There were no differences in function between descending and sigmoid colonic J-pouches. TME in a specialised colorectal unit has low morbidity and mortality. Our procedure of choice is that of a sigmoid colon J-pouch anal anastomosis.

Colorectal Neoplasms↗

PubMed1998

Total mesorectal excision for cancer of the rectum.

The concept of total mesorectal excision (TME) was first described by R. J. Heald in 1982 as a radical cancer operation based on the anatomy of fascial planes and fibrous spaces of the pelvis. The ampulla recti is invested by a fascia propria which is a part of the visceral pelvic fascia. The fascia propria is separated from the parietal pelvic fascia by the pelvirectal fibrous space, which is a compartment of the subperitoneal space of the pelvis. The lateral ligaments of the rectum divides the pelvirectal space into a prerectal and a retrorectal part. TME is defined as the resection of the rectum with its surrounding fatty and lymphatic tissue contained within the visceral sheet of the pelvic fascia. The dissection proceeds in the nearly avascular cleavage plane between the visceral and the parietal fascial sheets, allowing maximal protection of the hypogastric nerves and the inferior hypogastric plexus. Continuity of the prerectal and retrorectal parts of the field of dissection is established by dividing the lateral ligaments of the rectum slightly inside the point where they swing away from the parietal fascia of the pelvic side wall. By following this plane of dissection it is possible to achieve en bloc excision of the total mass of perirectal lymphatic and fatty tissue down to the pelvic floor.

Humans↗

PubMed2004

Current status and future prospects of sentinel node navigational surgery for gastrointestinal cancers.

Until the late 1990s, the application of the sentinel node (SN) concept to gastrointestinal (GI) malignancies was not recognized because of the multidirectional and complicated lymphatic flow from the GI tract. However, several studies supporting the validity of the SN concept for GI cancers have been reported in the past 5 years. Because of its anatomical location, gastric cancer is one of the most suitable targets for minimally invasive surgery based on SN status. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Although SNs in esophageal cancer are multiple and are distributed widely from the cervical to the abdominal area, selective and modified lymphadenectomy for clinically N0-stage esophageal cancer is likely to become feasible and clinically viable. Total mesorectal excision (TME) is accepted as a standard surgical procedure for rectal cancer. However, there is a risk of aberrant distribution of SNs beyond the extent of TME; for example, SNs may be lateral to the lower rectum. SN mapping with scintigraphy is useful for effective sampling of SNs in unexpected areas and accurate staging without extensive lymph node dissection. There are several practical issues to be overcome. The techniques and feasibility of laparoscopic SN sampling are still under investigation. Large-scale multicenter prospective validation studies for SN mapping in GI cancer are essential. If these remaining issues can be solved, SN mapping for GI cancer will have great clinical impact.

Biliary Tract Neoplasms↗

PubMed2003

[Total excision of the mesorectum in cancer of the lower and middle rectum. Oncological and functional results].

INTRODUCTION: The introduction of total mesorectal excision (TME) in the treatment of rectal cancer has improved survival rates and decreased recurrence. Our objective was to analyse perioperative data as well as the results of the follow-up examination. Risk-factors for local recurrence should be identified since the indication for adjuvant therapy in "optimal surgery" has to be redefined. PATIENTS AND METHODS: Between March 1997 and December 2001, 108 patients with adenocarcinoma of the lower and middle rectum were operated on by three surgeons according to the concept of total mesorectal excision. In 75 (69.4%) patients,a lower anterior resection and in 32 (29.2%) cases an abdominoperineal resection was performed. One patient received a Hartmann's resection. There were 15 cases of stage IV (UICC) present and in 53 patients the tumor extension was restricted to the wall. Demographic and perioperative data as well as the results of the follow-up examination were registered prospectively. The median follow-up period amounted to 24 months (2-56). RESULTS: A total of 87 patients underwent a curative resection. Fourteen lymph nodes were dissected (median). Pelvic autonomic nerve preservation was possible in 90 patients. The median intraoperative blood loss was 500 ml. As surgical complications, anastomotic leakage occurred in 18% of cases, perineal wound infection in 33%, and bladder dysfunction (requiring catheterisation) in 5.6%. The overall rate of recurrence was 17.5%. The rate of local recurrence was 4.9% and the survival rate was 91% over 3 years. Risk factors for local recurrence are N2-disease, transmural growth and tumor localisation in the lower third of the rectum. CONCLUSIONS: TME offers good oncological and functional results with low complication rates for the treatment of cancer in the middle and upper third of the rectum. Interdisciplinary multicenter studies are still necessary to redefine the place of adjuvant radiation and chemotherapy in cases of cancer in the lower two thirds of the rectum and stage III disease.

Adenocarcinoma↗

PubMed2026

Machine learning identifies ac4C-related prognostic signature and TUBA1C as therapeutic target in COAD.

To explore the role of N4-acetylcytidine (ac4C)-related genes (acRGs) in colon adenocarcinoma (COAD) and identify reliable prognostic biomarkers and potential therapeutic targets. Multi-source transcriptomic datasets (TCGA-COAD, GSE39582, GSE17536) and single-cell RNA-seq data were analyzed. Ten machine learning algorithms were integrated to construct an acRG-based prognostic signature (acRGBS). Immune microenvironment (TME) and genomic profiling were performed, with in vitro functional experiments validating TUBA1C's role. acRGBS, comprising four hub genes (SARAF, CDC42SE2, TSPYL2, TUBA1C), effectively stratified COAD patients into high- and low-risk groups with distinct survival outcomes and was an independent prognostic factor. High-risk patients exhibited increased genomic instability and immunosuppressive TME, while low-risk patients had favorable immunotherapy response. TUBA1C was overexpressed in COAD cells, and its knockdown inhibited proliferation/migration and induced apoptosis. The acRGBS is a robust prognostic tool for COAD, and TUBA1C serves as a candidate therapeutic target, providing new insights for personalized COAD management.

Humans↗

PubMed2005

"Fast-track" rehabilitation after rectal cancer resection.

BACKGROUND AND AIMS: After rectal cancer surgery, postoperative general complications occur in 25-35% of all patients and postoperative hospital stay is 14-21 days. "Fast-track" rehabilitation has been shown to accelerate recovery, reduce general morbidity and decrease hospital stay after elective colonic surgery. Because the feasibility of "fast-track" rehabilitation in patients undergoing rectal cancer surgery has not been demonstrated yet, we demonstrate our initial results of "fast-track" rectal cancer surgery. PATIENTS AND METHODS: Seventy consecutive unselected patients undergoing rectal cancer resection by one surgeon underwent a perioperative "fast-track" rehabilitation. Demographic and operative data, pulmonary function, pain and fatigue, local and general complications and mortality were assessed prospectively. RESULTS AND FINDINGS: Thirty-six female and 34 male patients aged 65 (34-77) years underwent open (n=31) or laparoscopic (n=39) anterior resection with partial mesorectal excision (PME 27), anterior resection with total mesorectal excision and protective loop ileostomy (TME 29) or abdominoperineal excision with colostomy (APR 14). Overall, pulmonary function returned to >80% of preoperative value on day 2 (1-4) and the first bowel movement occurred on day 1 (0-3) after surgery. The incidence of local and general complications was 27 and 18%, respectively. Postoperative hospital stay was 8 (3-50) days overall, but shorter after PME [5 (3-47)] than TME [10 (5-42)] or APR [9 (5-50)] (p<0.01). INTERPRETATION AND CONCLUSION: "Fast-track" rehabilitation was feasible in patients undergoing rectal cancer resection. Local morbidity was not increased, while general morbidity and postoperative hospital stay compared favourably to other series with "traditional" perioperative care.

Adult↗

PubMed2006

Prospective randomised trial comparing ileocaecal interposition and colon-J-pouch as rectal replacement after total mesorectal excision.

BACKGROUND: Ileocaecal interposition (ICI) is a technique of rectal replacement after total mesorectal excision (TME), but the method has never been evaluated in a randomised fashion. We performed a randomised, controlled trial to compare ICI and colon-J-pouch (CJP) for rectal replacements after TME for rectal cancer. MATERIALS AND METHODS: Fifteen patients were enrolled into each treatment group of the trial according to the protocol. Follow-up evaluations were performed 3 months and 1 year after ileostomy closure and at a mean of 5 years after initial surgery. RESULTS: Similar results between the groups were found for incontinence, urgency, constipation and quality of life at all follow-ups. The frequency of defecation was slightly lower in the CJP group at 3 months [3 (2-6) vs 5 (2-11) (p=0.043)] and at 1 year [3 (2-5) vs 5 (2-8) (p=0.034)]. However, this difference lost significance if patients who had postoperative radiotherapy were excluded from the analysis. Four out of the 15 patients treated with ICI experienced bowel obstruction, which required open surgery in two, endoscopic dilatation in one or maintenance of the ileostomy in one patient. None of the patients treated with CJP had similar complications. CONCLUSIONS: ICI and CJP reconstruction result in a similar functional outcome and quality of life. As ICI did not show any benefit over CJP and tended to result in a higher frequency of defecation, it should not be used as a first choice treatment. In addition, ICI was associated with significant complications after radiotherapy. Therefore, it must not be used if postoperative radiochemotheray is intended.

Adenocarcinoma↗

PubMed2006

Preoperative radiation therapy for locally advanced rectal cancer: a comparison between two different time intervals to surgery.

BACKGROUND: Although it is now considered a standard treatment to irradiate an advanced mid or low rectal tumor before surgical total mesorectal excision (TME), the optimal time interval between radiation therapy and surgery remains controversial. MATERIALS AND METHODS: Between 1995 and 2005, patients undergoing preoperative radiation therapy and TME for locally advanced mid and low rectal tumors treated in the VU Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment in the VU Medical Center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6-8 weeks in the VU Medical Center (LI group). Preoperative tumor staging, operative data, postoperative complications, pathology results, and follow-up were compared. RESULTS: The SI group (N=57) underwent surgery after a median delay of 4 days and the LI group (N=51) after 45 days. Operative data and short-term morbidity were comparable for both groups. However, significantly higher numbers of complete remissions (12 vs 0%), tumor downstaging (55 vs 26%), and less lymph-node metastases (22 vs 44%) were found in the LI group. No significant differences were found regarding local control or long-term survival after a median follow-up of 34 months. CONCLUSION: Several advantages, such as complete remissions and downstaging in the LI group, do not appear to have expression in a better survival or less local recurrences after a median follow-up of 34 months. Although larger (randomized) studies will be needed for definite conclusions, this may indicate that patients can be operated on within 2 weeks after radiation therapy.

Aged↗

PubMed2005

Patterns of neoplastic foci and lymph node micrometastasis within the mesorectum.

BACKGROUND AND AIMS: Local recurrence after rectal cancer surgery is conceived to result from microscopically incomplete resection. We aimed to investigate the patterns of mesorectal neoplastic foci, and examined the involvement and micrometastasis of lymph nodes. METHODS: Observation of large tissue slice and analysis of tissue microarray were integrated in the pathological study of 31 total mesorectal excision (TME) specimens. RESULTS: Altogether, 349 mesorectal neoplastic foci were examined from 18 specimens. Almost 33% of them were in the outer layer of mesorectum. Concerning position of primary tumor, ipsilateral neoplastic foci were significantly more than contralateral neoplastic foci. Distal mesorectal spread was found in four patients with the distance ranging from 1 to 3.5 cm. Four specimens were diagnosed to have circumferential margin involved. Nine hundred seventy-two lymph nodes were harvested with 128 involved by tumor. No significant difference in occurrence of micrometastasis was observed among tumors of different stage. CONCLUSIONS: Combination of large tissue slice and tissue microarray provided a more detailed method in studying the metastasis of rectal cancer. Complete excision of the mesorectum with fascia propria circumferentially intact is essential. Circumferential margin involvement and micrometastasis suggested that tumor spread may go beyond the scope of a single TME procedure.

Adenocarcinoma↗

PubMed2005

The transverse coloplasty pouch.

BACKGROUND: The introduction of the total mesorectal excision (TME) and the use of modern staplers have improved outcome and increased the rate of sphincter-preserving low anterior resections in rectal cancer. Consequently, the interest in functional results after rectal reservoir reconstruction increased significantly. METHODS: A review of the current literature was conducted on the development of colon pouch procedures with a particular focus on the transverse coloplasty pouch compared with the colon J-pouch and other current techniques of reconstruction after TME such as the side-to-end anastomosis. RESULTS: The colon J-pouch (CJP) became the "gold standard" for rectal reservoir reconstruction owing to better early functional results compared with the straight coloanal anastomosis (CAA). However, 30% of the patients with CJP faced late evacuation problems requiring the chronic use of enemas or laxatives. This rate could be decreased by shortening the limb of the CJP from 8-10 to 5-6 cm, but the late evacuation problems remained in approximately 10% of the patients. An overview of the current knowledge on technical and functional aspects as well as indications and results of the transverse coloplasty pouch (TCP) is presented. CONCLUSION: The TCP was developed to provide early functional results comparable to the CJP while avoiding the late evacuation problems. Functional results after TCP, small colon J-pouch and side-to-end anastomosis are similar. Evacuation problems after TCP have not been reported.

Colectomy↗

PubMed1998

Adjuvant radiochemotherapy--what is the patients benefit?

BACKGROUND: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. METHOD/PATIENTS: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. RESULTS: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II-III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11-18%, and survival rates significantly improved by 10-14%. Severe acute toxicities occurred in 50-61% of the patients, compromising compatibility, and caused death in 0-1%. Small-bowel obstruction leading to surgery was noted in 2-6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. CONCLUSION: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III.

Chemotherapy, Adjuvant↗

PubMed2006

Laparoscopic resection with intraoperative radiotherapy: a new step in the multimodal treatment of advanced colorectal cancer.

BACKGROUND: Local recurrence is one of the most important problems related to resection of rectal cancer in locally advanced cases (T3-T4). Total mesorectal excision (TME) is the mainstay of surgical therapy, although many articles have been published about the availability of intraoperative radiotherapy (IORT) for the control of locally advanced rectal cancers. METHODS: The authors describe six patients affected by advanced rectal cancer (T3N1) whom they treated with neoadjuvant radiochemotherapy and laparoscopic rectal resection combined with TME and IORT. RESULTS: The operative time did not exceed 6 h in any case with IORT treatment. The procedure itself and the transfer of patients to the radiotherapy room accounted for about 2 h. The postoperative course was uneventful in every case, and all the patients were discharged within the first 8 postoperative days. CONCLUSIONS: This report describes the technical aspect and the feasibility of IORT associated with laparoscopic surgical resection for rectal cancer.

Adult↗