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Niv E, Ovadia B, Groisman G, Kopelman Y. CMV-Induced Severe Colonic Stricture in an Adult Crohn's Disease Patient. Dig Dis Sci 2021; 66:636-639. [PMID: 32219611 DOI: 10.1007/s10620-020-06206-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 03/10/2020] [Indexed: 12/09/2022]
Affiliation(s)
- Eva Niv
- Meuhedet Health Services, Hillel-Yaffe Medical Center, Hadera, Israel.
| | - Baruch Ovadia
- Department of Gastroenterology, Hillel-Yaffe Medical Center, Hadera, Israel
| | - Gabriel Groisman
- Department of Pathology, Hillel-Yaffe Medical Center, Hadera, Israel
| | - Yael Kopelman
- Department of Gastroenterology, Hillel-Yaffe Medical Center, Hadera, Israel
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Liu B, Ge L, Wang J, Chen YQ, Ma SX, Ma PL, Zhang YQ, Yang KH, Cai H. Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis. World J Gastrointest Oncol 2021; 13:69-86. [PMID: 33510850 PMCID: PMC7805273 DOI: 10.4251/wjgo.v13.i1.69] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/06/2020] [Accepted: 12/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.
AIM To evaluate the value of IORT for patients with rectal cancer.
METHODS We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.
RESULTS In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000).
CONCLUSION The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.
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Affiliation(s)
- Bin Liu
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jing Wang
- Gansu University of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Ya-Qiong Chen
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Pei-Lan Ma
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Yun-Qiang Zhang
- Gansu Provincial Hospital, General Surgery Clinical Medical Center, Lanzhou 730000, Gansu Province, China
| | - Ke-Hu Yang
- Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
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Joechle K, Gkika E, Grosu AL, Lang SA, Fichtner-Feigl S. Intraoperative Strahlentherapie – Indikationen und Optionen in der Viszeralchirurgie. Chirurg 2020; 91:743-754. [DOI: 10.1007/s00104-020-01179-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Zusammenfassung
Hintergrund
Die intraoperative Strahlentherapie (IORT) ermöglicht durch die chirurgische Exposition des Tumors und des Tumorbetts eine hohe Präzision, welche eine hohe Strahlendosis im Bereich des Tumors zulässt und gleichzeitig gesundes Gewebe als den dosislimitierenden Faktor vor Strahlung schützt. Aus diesem Grund bietet die IORT besonders dann einen Vorteil, wenn die lokale Tumorkontrolle das Langzeitüberleben entscheidend beeinflusst und Funktionserhalt ermöglicht.
Ziel der Arbeit
Die in dieser Übersichtsarbeit aufgearbeiteten Erkenntnisse aus der Literaturrecherche erlauben einen evidenzbasierten Umgang hinsichtlich Indikationen und Therapieoptionen der IORT für intraabdominelle Tumoren.
Ergebnisse und Schlussfolgerung
Die Effektivität der IORT kann anhand der vorhandenen Evidenzlage nicht abschließend beurteilt werden, jedoch ist die IORT als Ergänzung der multimodalen Therapie bei (Rezidiv‑)Rektumkarzinomen und Sarkomen aktiv im klinischen Alltag etabliert. Magen- und Pankreaskarzinome stellen weitere Indikationen dar; ergänzende Studien sind jedoch notwendig, um die Rolle der IORT hier klar zu definieren. Ein wesentlicher Faktor, damit für Patienten mit primärem Karzinom und insbesondere für Patienten mit lokalem Rezidiv verbesserte lokale Rezidiv- und Überlebensraten erreicht werden können, scheint die Patientenselektion zu sein.
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Potemin S, Kübler J, Uvarov I, Wenz F, Giordano F. Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy. Radiat Oncol 2020; 15:11. [PMID: 31924250 PMCID: PMC6954580 DOI: 10.1186/s13014-020-1458-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 01/05/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Neoadjuvant external-beam radiotherapy (EBRT) with concomitant chemotherapy is the current standard-of-care for locally-advanced rectal cancer. Intraoperative radiotherapy (IORT) is to date only recommended for pelvic recurrences or incompletely resectable tumors. We here report on patients with stage II/III rectal cancer that were treated with IORT in a regional Russian university center due to limited access to EBRT. METHODS We retrospectively analyzed data from patients that were diagnosed with locally-advanced rectal cancer and underwent surgery from December 2012 to October 2016 at a regional oncological center in Russia (Krasnodar). During this period, access to EBRT was limited due to a temporary lack of a sufficient number of EBRT facilities. Patients unable to travel to a distant radiotherapy site received IORT alone, those that could travel received neoadjuvant external beam (chemo-) radiotherapy. Factors of interest were tumor stage, tumor differentiation, resection status, surgery type and neoadjuvant or adjuvant chemotherapy. We assessed local progression-free survival (L-PFS), PFS and overall survival (OS). RESULTS A total of 172 patients were included in this analysis. Of those, 92 (53.5%) were treated with IORT alone (median dose: 15 Gy [8.4-17 Gy]) and 80 (46.5%) received both neoadjuvant EBRT (median dose: 50.4 Gy [40-50.4 Gy]) and IORT (median dose: 15 Gy [15-17 Gy]). The median age was 65 years [33-82]. The median follow-up was 23 months [0-63 months]. The incidence of toxicity was low in both groups with an overall complication rate of 5.4%. Local PFS at 4 years was comparable with 59.4% in the IORT group and 65.4% in the IORT/EBRT group (p = 0.70). Similarly, there was no difference in OS or PFS (p = 0.66, p = 0.51, respectively). CONCLUSIONS IORT is a valuable option for patients with locally-advanced rectal cancer in the absence of access to EBRT.
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Affiliation(s)
- Sergey Potemin
- Department of Colorectal Surgery, Regional Oncological Center of Krasnodar, Krasnodar, Russia
| | - Jens Kübler
- Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Ivan Uvarov
- Department of Colorectal Surgery, Regional Oncological Center of Krasnodar, Krasnodar, Russia
| | - Frederik Wenz
- Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Frank Giordano
- Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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Hissong E, Chen Z, Yantiss RK. Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence. Mod Pathol 2019; 32:1210-1216. [PMID: 30952971 DOI: 10.1038/s41379-019-0258-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/30/2019] [Accepted: 01/31/2019] [Indexed: 02/07/2023]
Abstract
Cytomegalovirus promotes mucosal injury in patients with inflammatory bowel disease, historically affecting 10-25% of ulcerative colitis patients with refractory disease. Viral reactivation is likely related to long-term corticosteroid therapy, which is no longer central to maintenance of patients with inflammatory bowel disease. We hypothesize that viral detection rates have decreased in the modern era, reflecting widespread use of immunomodulatory agents to control inflammation. We performed this study to evaluate the relationships between medical regimens and cytomegalovirus detection rates among patients with inflammatory bowel disease. We searched our database for all patients with established inflammatory bowel disease and severe flares diagnosed from 2002 to 2017. Patients maintained with corticosteroid therapy were considered to be corticosteroid-dependent and those treated with other agents were classified as corticosteroid-independent, provided they had not received corticosteroids within 6 months of colonoscopy. Biopsy samples were reviewed for viral inclusions and subjected to cytomegalovirus immunohistochemistry, and rates of viral detection were compared between groups. There were 135 corticosteroid-dependent patients; most had ulcerative colitis flares occurring during the 2002-2009 period. Patients with ulcerative colitis and Crohn disease were equally represented in the corticosteroid-independent group (n = 133) and most were evaluated for disease flares during the 2010-2017 interval. Cytomegalovirus was detected in 13 (8%) cases; 9 (69%) were diagnosed from 2002 to 2009 and all were obtained from corticosteroid-dependent patients (p = < 0.001). We conclude that rates of cytomegalovirus-related enterocolitis are declining among inflammatory bowel disease patients, reflecting a shift away from corticosteroid-based maintenance therapy in favor of more effective agents that do not promote viral reactivation.
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Affiliation(s)
- Erika Hissong
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
| | - Zhengming Chen
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY, USA
| | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
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Mavropoulou E, Ternes K, Mechie NC, Bremer SCB, Kunsch S, Ellenrieder V, Neesse A, Amanzada A. Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome. BMJ Open Gastroenterol 2019; 6:e000258. [PMID: 30899538 PMCID: PMC6398871 DOI: 10.1136/bmjgast-2018-000258] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 12/27/2018] [Accepted: 12/28/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality. METHODS A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome. RESULTS The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status. CONCLUSIONS In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.
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Affiliation(s)
- Eirini Mavropoulou
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Kristin Ternes
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Nicolae-Catalin Mechie
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | | | - Steffen Kunsch
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Volker Ellenrieder
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Albrecht Neesse
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Ahmad Amanzada
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
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Cytomegalovirus infection and steroid-refractory inflammatory bowel disease: possible relationship from an updated meta-analysis. Ir J Med Sci 2018; 187:935-942. [DOI: 10.1007/s11845-018-1752-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Accepted: 01/17/2018] [Indexed: 12/19/2022]
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Pilar A, Gupta M, Ghosh Laskar S, Laskar S. Intraoperative radiotherapy: review of techniques and results. Ecancermedicalscience 2017; 11:750. [PMID: 28717396 PMCID: PMC5493441 DOI: 10.3332/ecancer.2017.750] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Indexed: 12/14/2022] Open
Abstract
Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community. Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise. IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers). This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.
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Affiliation(s)
- Avinash Pilar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Meetakshi Gupta
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Sarbani Ghosh Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Siddhartha Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
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Beswick L, Ye B, van Langenberg DR. Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis. Inflamm Bowel Dis 2016; 22:2966-2976. [PMID: 27763950 DOI: 10.1097/mib.0000000000000958] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented. RESULTS This review discusses the concept of CMV reactivation which frequently occurs in inflammatory bowel disease-related colitis, most commonly in those presenting with steroid-refractory colitis. In this context, although signifying a poorer prognosis, in most cases, the virus is nonpathogenic and thus antiviral treatment is unhelpful. However, when reactivation gives rise to true CMV disease (colitis) as best discriminated by histology with immunohistochemistry (and the density of such) in colonic biopsy tissue, the patient does benefit from antivirals. CONCLUSION Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.
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Affiliation(s)
- Lauren Beswick
- *Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia; and †Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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Pai VD, Jatal S, Ostwal V, Engineer R, Arya S, Patil P, Bal M, Saklani AP. Multivisceral resections for rectal cancers: short-term oncological and clinical outcomes from a tertiary-care center in India. J Gastrointest Oncol 2016; 7:345-353. [PMID: 27284465 PMCID: PMC4880780 DOI: 10.21037/jgo.2016.01.02] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 11/20/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Locally advanced rectal cancers (LARCs) involve one or more of the adjacent organs in upto 10-20% patients. The cause of the adhesions may be inflammatory or neoplastic, and the exact causes cannot be determined pre- or intra-operatively. To achieve complete resection, partial or total mesorectal excision (TME) en bloc with the involved organs is essential. The primary objective of this study is to determine short-term oncological and clinical outcomes in these patients undergoing multivisceral resections (MVRs). METHODS This is a retrospective review of a prospectively maintained database. Between 1 July 2013 and 31 May 2015, all patients undergoing MVRs for adenocarcinoma of the rectum were identified from this database. All patients who had en bloc resection of an adjacent organ or part of an adjacent organ were included. Those with unresectable metastatic disease after neoadjuvant therapy were excluded. RESULTS Fifty-four patients were included in the study. Median age of the patients was 43 years. Mucinous histology was detected in 29.6% patients, and signet ring cell adenocarcinoma was found in 24.1% patients. Neoadjuvant therapy was given in 83.4% patients. R0 resection was achieved in 87% patients. Five-year overall survival (OS) was 70% for the entire cohort of population. CONCLUSIONS In Indian subcontinent, MVRs in young patients with high proportion of signet ring cell adenocarcinomas based on magnetic resonance imaging (MRI) of response assessment (MRI 2) is associated with similar circumferential resection margin (CRM) involvement and similar adjacent organ involvement as the western patients who are older and surgery is being planned on MRI 1 (baseline pelvis). However, longer follow-up is needed to confirm noninferiority of oncological outcomes.
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Lee HS, Park SH, Kim SH, Kim J, Choi J, Lee HJ, Kim WS, Lee JM, Kwak MS, Hwang SW, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yoon YS, Yu CS, Kim JH, Yang SK. Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis. Inflamm Bowel Dis 2016; 22:912-918. [PMID: 26829410 DOI: 10.1097/mib.0000000000000675] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS We retrospectively analyzed patients with ASUC from 2011 to 2014 according to the criteria of Truelove and Witts. CMV colitis was diagnosed by histopathological and/or immunohistochemical analysis of tissue samples. The risk factors for CMV colitis were investigated and clinical outcomes were assessed using the rate of rescue therapy and colectomy. RESULTS Of 149 patients with ASUC, 50 (33.6%) were diagnosed with CMV colitis. During admission, 16 of 149 patients (10.7%) underwent colectomy: 7 of 50 (14.0%) in the ASUC-CMV group versus 9 of 99 (9.1%) in the ASUC-only group (P = 0.364). The need for rescue therapy was 2.28-fold higher in the ASUC-CMV group than in the ASUC-only group in multivariate analysis (95% confidence interval, 1.10-4.72). Multivariate analysis also revealed that recent use of high-dose steroids (odds ratio, 3.30; 95% confidence interval, 1.33-8.19) and a higher Mayo score (odds ratio, 1.58; 95% confidence interval, 1.05-2.38) were risk factors for CMV colitis. CONCLUSIONS CMV colitis often occurs in ASUC, particularly in patients who have recently been treated with high-dose steroids and have a higher Mayo score on admission. Patients with ASUC and CMV colitis seem to have a poorer prognosis, as indicated by the greater need for rescue therapy.
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Affiliation(s)
- Ho-Su Lee
- *Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; and Departments of †Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ‡Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, §Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, and ‖Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus: Systematic Review and Meta-analysis. Inflamm Bowel Dis 2015. [PMID: 26197450 DOI: 10.1097/mib.0000000000000489] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The role of antiviral therapy in patients with ulcerative colitis (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a systematic review and meta-analysis to assess the association between antiviral therapy and the risk of colectomy. METHODS Multiple electronic databases were searched systematically through July 2014 for studies reporting the risk of colectomy in patients with UC with CMV stratified by treatment with antiviral agents. Colectomy rates were assessed for the overall cohort and stratified by corticosteroid (CS) refractoriness. We estimated summary odds ratios and 95% confidence intervals, using random-effects model, and used Grading of Recommendations Assessment, Development, and Evaluation criteria to appraise the quality of evidence. RESULTS Fifteen observational studies (333 patients with UC with CMV, 43.2% treated with antiviral agents) were identified, of which 8 stratified patients according to CS-refractory disease (55.4% treated with antiviral agents). Antiviral therapy resulted in a significantly lower risk of colectomy in patients with CS-refractory disease (odds ratio, 0.20; 95% confidence interval, 0.08-0.49; I = 0%) but not in the overall population of patients with UC (odds ratio, 0.92; 95% confidence interval, 0.31-2.76; I = 65). The quality evidence was low. The results were stable when restricting the analysis to patients with a tissue diagnosis of CMV and studies that defined CS-refractory disease as a failure to respond to intravenous CS. CONCLUSIONS Antiviral therapy may benefit a subgroup of patients with UC who are refractory to CS. Further prospective trials are required to confirm these findings.
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Wu XW, Wu L, Ji HZ, Wang FY. Relationship Between Cytomegalovirus Infection and Steroid Resistance in Inflammatory Bowel Disease: A Meta-Analysis. Dig Dis Sci 2015; 60:3203-8. [PMID: 26031424 PMCID: PMC4621704 DOI: 10.1007/s10620-015-3733-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 05/24/2015] [Indexed: 01/30/2023]
Abstract
BACKGROUND AND AIMS Steroid resistance presents an administration difficulty in inflammatory bowel disease (IBD). The reason of steroid resistance is still unclear, but cytomegalovirus (CMV) infection may be a potential cause in some IBD patients. We carried out a meta-analysis to investigate the relationship between CMV infection and steroid-resistant IBD. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched up to June 2014, with no language restrictions, for observational studies. Additional references were obtained from reviewed articles. RESULTS Eleven studies involving 867 IBD patients were included in the meta-analysis. Steroid resistance rate was 70.0% in CMV-positive IBD patients, which was significantly higher than that in CMV-negative IBD patients (RR = 2.12, 95% CI = 1.72-2.61). There was significant heterogeneity in the included eleven studies (I (2) = 57.6%). When the only one study with a few patients was excluded, sensitivity analysis suggested a similar outcome (RR = 2.07, 95% CI = 1.80-2.39, 10 studies). Based on the funnel plot and Egger's test, we considered that there was a probable publication bias. CONCLUSION Our meta-analysis suggests that CMV-positive IBD patients have a nearly double risk of steroid resistance compared with CMV-negative IBD patients, indicating that CMV infection is a probable cause of steroid-resistant IBD.
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Affiliation(s)
- Xiao-wei Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002 Jiangsu Province China
| | - Lin Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002 Jiangsu Province China
| | - Hong-zan Ji
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002 Jiangsu Province China
| | - Fang-yu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002 Jiangsu Province China
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Landsman MJ, Sultan M, Stevens M, Charabaty A, Mattar MC. Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn's disease patients. Inflamm Bowel Dis 2014; 20:2503-2510. [PMID: 25208106 DOI: 10.1097/mib.0000000000000140] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, stretches beyond control of flares. Some infections of the gastrointestinal tract are more commonly seen in patients with IBD. Work from the Human Microbiome Project has been instrumental in our understanding of the interplay between the vast gut microbiota and host immune responses. Patients with IBD may be more prone to infectious complications based on their underlying inflammatory disease and variations in their microbiome. Immunosuppressant medications commonly used to treat patients with Crohn's and colitis also play a role in predisposing these patients to acquire these infections. Here, we present a detailed review of the data focusing on the most common infections of the gastrointestinal tract in patients with IBD: Clostridium difficile infections (CDI) and cytomegalovirus (CMV). We will discuss appropriate diagnostic tools and treatment options for these infections. Other less common infections will also be reviewed briefly. Studying the various infections of the gastrointestinal tract in these patients could enhance our understanding of the pathophysiology of IBD.
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Affiliation(s)
- Marc J Landsman
- *Internal Medicine, Georgetown University Hospital, Washington, DC; †Division of Gastroenterology, Georgetown University Hospital, Washington, DC; and ‡Division of Infectious Diseases, Virginia Commonwealth University Medical Center, Richmond, Virginia
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15
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Seo HI, Park DI, Kim TO, Kim YS, Lee SH, Kim JW, Kim JH, Shin JE. The effect of infliximab on patients with ulcerative colitis in Korea. Intest Res 2014; 12:214-20. [PMID: 25349595 PMCID: PMC4204725 DOI: 10.5217/ir.2014.12.3.214] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Revised: 02/28/2014] [Accepted: 03/02/2014] [Indexed: 12/26/2022] Open
Abstract
Background/Aims Infliximab was introduced recently as a rescue therapy for ulcerative colitis (UC) patients refractory to conventional treatments such as therapy with 5-amiono salicylic acids (5-ASA), immune modulators, and corticosteroids. However, there is insufficient data about its efficacy and safety in Korea. Methods From 7 tertiary referral hospitals, 33 patients who were treated with infliximab for moderate to severe (Mayo score 6-12) UC refractory to conventional treatment were recruited to this study. Clinical remission was defined as a total Mayo score of 2 or lower and every subscore less than 2. Partial response was defined as a decrease of Mayo score at least 3 points from baseline. Results Twenty-three patients (69.7%) showed clinical remission and 29 patients (87.8%) showed partial response in the observation period. When the remission and non-remission groups were compared in univariate analysis, only a higher total Mayo score at base line (11.0±0.9 vs. 9.9±1.5; P=0.04) was related to remission. The remission maintenance rate decreased with time in the Kaplan-Meier analysis. Two patients experienced re-remission after the first remission followed by aggravation during infliximab treatment. Three patients stopped infliximab treatment owing to adverse events including rhabdomyolysis, pneumonia, and fever of unknown origin. Conclusions If there is no choice except surgery for UC patients refractory to conventional treatment, infliximab is an effective and relatively safe treatment option for these patients in Korea.
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Affiliation(s)
- Hyun Il Seo
- Department of Internal Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, Korea
| | - Dong Il Park
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea
| | - Tae Oh Kim
- Department of Internal Medicine, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Korea
| | - You Sun Kim
- Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul, Korea
| | - Suck-Ho Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul, Korea
| | - Jae Hak Kim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
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Wiig JN, Giercksky KE, Tveit KM. Intraoperative radiotherapy for locally advanced or locally recurrent rectal cancer: Does it work at all? Acta Oncol 2014; 53:865-76. [PMID: 24678823 DOI: 10.3109/0284186x.2014.895037] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Intraoperative radiotherapy (IORT) has been given for primary and locally recurrent rectal cancer for 30 years. Still, its effect is not clear. MATERIAL AND METHODS PubMed and EMBASE search for papers after 1989 on surgical treatment and external beam radiotherapy (EBRT) for primary advanced and locally recurrent rectal cancer, with and without IORT. From each center the most recent paper was generally selected. Survival and local recurrence at five years was tabulated for the total groups and separate R-stages. Also, the technique for IORT, use of EBRT and chemotherapy as well as surgical approach was registered. RESULTS In primary cancer 18 papers from 14 centers were tabulated, including one randomized and five internally comparing studies, as well as seven studies without IORT. In locally recurrent cancer 18 papers from 13 centers were tabulated, including four internally comparing studies and also five without IORT. Overall survival (OS) and local recurrence rate (LRR) were higher for primary cancer compared to recurrent cancer. Patients with R0 resections had better outcome than patients with R1 or R2 resections. For primary cancer OS and LR rate of the total groups and R0 stages was not influenced by IORT. An effect on R1/R2 stages cannot be excluded. The only randomized study (primary cancer) did not show any effect of IORT. CONCLUSION IORT does not convincingly improve OS and LR rate for primary and locally recurrent rectal cancer. If there is an effect of IORT, it is small and cannot be shown outside randomized studies analyzing the separate R stages.
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Affiliation(s)
- Johan N Wiig
- Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway
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Olaisen M, Rydning A, Martinsen TC, Nordrum IS, Mjønes P, Fossmark R. Cytomegalovirus infection and postoperative complications in patients with ulcerative colitis undergoing colectomy. Scand J Gastroenterol 2014; 49:845-52. [PMID: 24947587 DOI: 10.3109/00365521.2014.929172] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Ulcerative colitis (UC) can be complicated by reactivation of cytomegalovirus (CMV). CMV reactivation may change the course of UC and may require antiviral treatment. Some risk factors of CMV reactivation have previously been identified, whereas the association between CMV reactivation and postoperative complications has not been examined systematically. METHODS Patients with UC operated with colectomy due to active UC were studied (n = 77). Patient and disease characteristics, as well as postoperative complications were recorded and CMV was detected by immunohistochemical examination of multiple sections from the colectomy specimen. RESULTS CMV was found in nine (11.7%) colectomy specimens. CMV-positive patients received significantly higher doses of corticosteroids at colectomy than CMV-negative patients (61.1 ± 23 vs 32.5 ± 32 mg/day, p = 0.01). CMV-positive patients were also older, had a higher risk of severe complications, higher American Society of Anesthesiologists (ASA) score, longer preoperative stay, and a higher rate of acute surgery. Complications occurred in 30 (39%) patients after surgery, 8(10.4%) of whom were serious. Two CMV-positive patients (2.6%) died in-hospital after the colectomy. High ASA score was associated with the occurrence of serious complications. CONCLUSION A relatively small proportion of patients with UC operated by colectomy were CMV positive. CMV positivity was associated with old age, high dose of corticosteroids at operation, high ASA score, acute surgery, and severe postoperative complications. Patients with such characteristics may be at risk of CMV infection and may require special management.
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Affiliation(s)
- Maya Olaisen
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU) , Trondheim , Norway
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Alberda WJ, Verhoef C, Nuyttens JJ, van Meerten E, Rothbarth J, de Wilt JHW, Burger JWA. Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2014; 88:1032-40. [PMID: 24661656 DOI: 10.1016/j.ijrobp.2014.01.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 01/07/2014] [Accepted: 01/10/2014] [Indexed: 01/15/2023]
Abstract
PURPOSE Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. METHODS AND MATERIALS All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. RESULTS A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) CONCLUSION: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.
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Affiliation(s)
- Wijnand J Alberda
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Joost J Nuyttens
- Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Joost Rothbarth
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Division of Surgical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - Jacobus W A Burger
- Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
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Abstract
Since the early 1990s, great efforts have been made in the field of human cytomegalovirus (HCMV) diagnosis. Besides HCMV diagnosis in immunosuppressed patients (solid organ transplant recipients, hematopoietic stem cell transplant patients and AIDS patients), diagnosis in connection with congenital HCMV infection is of great interest. This review focuses on the development and clinical utility of serological assays, as well as on virological tests (molecular and nonmolecular assays). Interpretation of these tests is strongly dependent on the patient group (solid organ transplant recipients and hematopoietic stem cell transplant patients) and whether the tests are used for screening, risk stratification or diagnosis. Furthermore, a better understanding of HCMV infection has led to new approaches in HCMV diagnosis and monitoring. Thus, assays for viral resistance testing and assays for monitoring the HCMV-specific cellular immune response are increasingly important for the guidance of antiviral therapy.
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Abstract
BACKGROUND Up to 30% of cases of pouchitis are felt to have a secondary cause. Cytomegalovirus (CMV) may represent a possible etiopathological agent. Here, we report our experience with CMV involvement of the pouch, including risk factors, clinical features, and pouch outcomes in patients with inflammatory bowel disease after proctocolectomy with ileal pouch-anal anastomosis. METHODS The pathology database at Mayo Clinic in Rochester was searched between January 1995 and October 2012 for patients with a tissue diagnosis of CMV of the pouch following ileal pouch-anal anastomosis. RESULTS Seven patients with CMV inclusions of the pouch were identified. The median age was 35 (range, 10-53) years, and the majority were female (71%). Five patients (71%) were on immunosuppressive medications including 4 who had undergone orthotopic liver transplantation for primary sclerosing cholangitis. The clinical presentation was similar among all patients: the majority had diarrhea (86%), fever (71%), and abdominal pain (57%). All had mucosal inflammation, with 71% having focal ulcerations in the pouch and 60% having inflammatory changes in the prepouch ileum. All patients improved with ganciclovir. None required pouch excision or had recurrent CMV infection. Three patients had recurrent nonspecific pouchitis. CONCLUSIONS A high index of suspicion is needed to diagnose CMV of the pouch. An increase in stool frequency and fever in patients on immune suppression or in those who have failed empiric antibiotics should prompt assessment for CMV infection. Antiviral therapy seems to be effective, and postinfection pouch outcomes seem favorable, particularly in those presenting with their first episode of pouchitis.
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Looking for endoscopic features of cytomegalovirus colitis: a study of 187 patients with active ulcerative colitis, positive and negative for cytomegalovirus. Inflamm Bowel Dis 2013; 19:1156-63. [PMID: 23619714 DOI: 10.1097/mib.0b013e31828075ce] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) is frequently detected in ulcerative colitis (UC) lesions of steroid-refractory patients. This has led to the suspicion that CMV might cause colitis and steroid refractoriness. METHODS During 2003 and 2011, 187 consecutive patients were divided into group I (n = 105), corticosteroid-free and thiopurine-free in the past 6 months, and group II (n = 82), all corticosteroid refractory. The combination of serum CMV immunoglobulin (Ig)M, CMV IgG, CMV antigenemia (Ag), and real-time polymerase chain reaction assays were performed to identify CMV(+) patients. RESULTS In group I, 79 patients were CMV IgG(+) and 26 patients were CMV IgG(-) and CMV IgM(-). In group II, 61 patients were CMV IgG(+), 1 CMV IgM(+), and 20 CMV IgG(-) and CMV IgM(-). All CMV IgG(+) patients were screened for CMV Ag. In group I, 6 of the 79 CMV IgG(+) patients were CMV Ag(+). In group II, 27 patients were CMV Ag(+). Colonoscopy was performed in all patients before screening for CMV. Similar colonoscopic features including punched out ulcers, geographic ulcers, and irregular ulcers were found in both CMV(+) and CMV(-) patients, without any striking difference between the 2 groups. CONCLUSIONS CMV reactivation might be encouraged by immunosuppressive drugs, like corticosteroids, immunomodulators, and therefore, patients with UC are at a high risk of CMV reactivation, potentially exacerbating UC. However, this study of 187 patients, CMV(+) and CMV(-), could not find colonoscopic features unique to CMV, except that CMV might be one factor for steroid refractoriness, and UC exacerbation.
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Mirnezami R, Chang GJ, Das P, Chandrakumaran K, Tekkis P, Darzi A, Mirnezami AH. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol 2013; 22:22-35. [PMID: 23270946 PMCID: PMC4663079 DOI: 10.1016/j.suronc.2012.11.001] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Revised: 11/03/2012] [Accepted: 11/10/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND The precise contribution of IORT to the management of locally advanced and recurrent colorectal cancer (CRC) remains uncertain. We performed a systematic review and meta-analysis to assess the value of IORT in this setting. METHODS Studies published between 1965 and 2011 that reported outcomes after IORT for advanced or recurrent CRC were identified by an electronic literature search. Studies were assessed for methodological quality and design, and evaluated for technique of IORT delivery, oncological outcomes, and complications following IORT. Outcomes were analysed with fixed-effect and random-effect model meta-analyses and heterogeneity and publication bias examined. RESULTS 29 studies comprising 14 prospective and 15 retrospective studies met the inclusion criteria and were assessed, yielding a total of 3003 patients. The indication for IORT was locally advanced disease in 1792 patients and locally recurrent disease in 1211 patients. Despite heterogeneity in methodology and reporting practice, IORT is principally applied for the treatment of close or positive margins. When comparative studies were evaluated, a significant effect favouring improved local control (OR 0.22; 95% CI = 0.05-0.86; p = 0.03), disease free survival (HR 0.51; 95% CI = 0.31-0.85; p = 0.009), and overall survival (HR 0.33; 95% CI = 0.2-0.54; p = 0.001) was noted with no increase in total (OR 1.13; 95% CI = 0.77-1.65; p = 0.57), urologic (OR 1.35; 95% CI = 0.84-2.82; p = 0.47), or anastomotic complications (OR 0.94; 95% CI = 0.42-2.1; p = 0.98). Increased wound complications were noted after IORT (OR 1.86; 95% CI = 1.03-3.38; p = 0.049). CONCLUSIONS Despite methodological weaknesses in the studies evaluated, our results suggest that IORT may improve oncological outcomes in advanced and recurrent CRC.
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Affiliation(s)
- Reza Mirnezami
- Section of Biosurgery & Surgical Technology, Department of Surgery & Cancer, Imperial College London, 10th Floor QEQM Building, St Mary's Hospital, London W2 1NY, UK
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Jiang Y, Ji X, Zhao S, Zhao R, Jin Y. Laparoscopic resection with intraoperative radiotherapy for local advanced rectal cancer: a preliminary case report. J Laparoendosc Adv Surg Tech A 2013; 23:267-70. [PMID: 23272726 DOI: 10.1089/lap.2012.0286] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE To report the feasibility of laparoscopic resection with intraoperative radiotherapy for local advanced rectal cancer in an Asian man. PATIENT AND METHODS A 55-year-old man with adenocarcinoma of the rectum presented at Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. The tumor, with a size of 5 × 5 cm, was located 3 cm from the anus and covered a circular area around approximately two-thirds of the bowel. The carcinoembryonic antigen level was 29.86 ng/mL; a nodule was detected, but no distant metastasis was detected. Preoperative staging was T4N1M0. After the patient signed the consent form, laparoscopic resection with intraoperative radiotherapy was performed. RESULTS The operation time was about 180 minutes, intraoperative blood loss was 100 mL, and postoperative hospital stay was 8 days. The patient had no postoperative complications. conclusions: Performance of laparoscopic resection with intraoperative radiotherapy for local advanced rectal cancer is feasible in selected patients.
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Affiliation(s)
- Yimei Jiang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Abstract
BACKGROUND Approximately 10% of patients with colorectal cancer have locally advanced disease with peritoneal involvement (T4a) or invasion of adjacent organs (T4b) at the time of diagnosis. Of patients who undergo resection with curative intent, between 7 and 33% develop isolated locoregional recurrences. R0 surgical excision is potentially curative. METHODS We reviewed the literature relating to multivisceral resection for T4 or recurrent colorectal cancer. RESULTS Comprehensive staging to identify the local and systemic extent of disease is essential to determine resectability and patient suitability for a curative approach. PET scans and pelvic MRI (rectal) staging and a coordinated multispecialty input to neoadjuvant treatment, multivisceral surgical resection, reconstruction and adjuvant chemotherapy are essential. Intraoperative radiotherapy and hyperthermic intraperitoneal chemotherapy may have a role in selected patients. R0 resection can achieve 5-year local control rates for primary locally advanced and recurrent colorectal cancer of up to 89 and 38%, respectively, and overall 5-year survival up to 66 and 25%, respectively. CONCLUSION An aggressive surgical strategy as part of a multimodal strategy in the treatment of locally advanced or recurrent colorectal cancer in the absence of incurable metastatic disease affords the best prospect for long-term survival in selected patients.
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Affiliation(s)
- J O Larkin
- Surgical Professorial Unit, St. Vincent's University Hospital and UCD School of Medicine and Medical Sciences, Dublin, Ireland
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25
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Varani S, Landini MP. Cytomegalovirus-induced immunopathology and its clinical consequences. HERPESVIRIDAE 2011; 2:6. [PMID: 21473750 PMCID: PMC3082217 DOI: 10.1186/2042-4280-2-6] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2011] [Accepted: 04/07/2011] [Indexed: 12/23/2022]
Abstract
Human cytomegalovirus (CMV) is a ubiquitous DNA virus that causes severe disease in patients with immature or impaired immune systems. During active infection, CMV modulates host immunity, and CMV-infected patients often develop signs of immune dysfunction, such as immunosuppression and autoimmune phenomena. Furthermore, active viral infection has been observed in several autoimmune diseases, and case reports have linked primary CMV infection and the onset of autoimmune disorders. In addition, CMV infection promotes allograft rejection and graft-versus-host disease in solid organ and bone marrow transplant recipients, respectively, further implicating CMV in the genesis and maintenance of immunopathological phenomena. The mechanisms by which CMV could induce inhibition of host defense, inflammation, and autoimmunity are discussed, as is the treatment of virus-induced immunopathology with antivirals.
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Affiliation(s)
- Stefania Varani
- Section of Microbiology, Department of Hematology and Oncology, University of Bologna, Bologna, Italy
| | - Maria Paola Landini
- Section of Microbiology, Department of Hematology and Oncology, University of Bologna, Bologna, Italy
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de Campos-Lobato LF, Stocchi L, da Luz Moreira A, Geisler D, Dietz DW, Lavery IC, Fazio VW, Kalady MF. Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 2011; 18:1590-8. [PMID: 21207164 DOI: 10.1245/s10434-010-1506-1] [Citation(s) in RCA: 149] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the clinical implications of pathologic complete response (pCR) (i.e., T0N0M0) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer. MATERIALS AND METHODS A single-center, prospectively maintained colorectal cancer database was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007. Patients were stratified into pCR and no-pCR groups and compared with respect to demographics, tumor and treatment characteristics, and oncologic outcomes. Outcomes evaluated were 5-year overall survival, disease-free survival, disease-specific mortality, local recurrence, and distant recurrence. RESULTS The query returned 238 patients (73% male), with a median age of 57 years and median follow-up of 54 months. Of these, 58 patients achieved pCR. Patients with pCR vs no-pCR were statistically comparable with respect to demographics, chemoradiation regimens, tumor distance from anal verge, clinical stage, surgical procedures performed, and follow-up time. No patient with pCR had local recurrence. Overall survival and distant recurrence were also significantly improved for patients achieving pCR. CONCLUSIONS Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer. Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population.
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Harris DA, Davies M, Lucas MG, Drew P, Carr ND, Beynon J. Multivisceral resection for primary locally advanced rectal carcinoma. Br J Surg 2010; 98:582-8. [PMID: 21656723 DOI: 10.1002/bjs.7373] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2010] [Indexed: 01/30/2023]
Abstract
BACKGROUND Pelvic multivisceral resection offers the possibility of cure in patients with locally advanced rectal cancer. This study assessed the clinical outcome and determinants of survival and local recurrence in patients undergoing multivisceral resection for clinical T4 primary rectal cancer. METHODS This was a cohort study of consecutive multivisceral resections carried out in a single centre from 2000 to 2009. Determinants of local recurrence and survival were examined by means of Kaplan-Meier survival curves and Cox regression analysis. RESULTS The study included 42 patients, with a median age of 62 (range 41-83) years, who underwent surgery with a median follow-up of 30 (range 2-102) months. Thirty-one patients had preoperative chemoradiotherapy. Seven patients had rectal resection with en bloc radical prostatectomy. The 30-day mortality rate was zero. Thirty-nine of the 42 patients had a negative circumferential resection margin. The 5-year overall survival rate for those who had complete resection was 48 per cent. Local recurrence was predicted by metastatic disease (P < 0.001) and nodal disease (P < 0.001), but not positive resection margins (P = 0.077). CONCLUSION An aggressive surgical strategy with complete resection is predictive of long-term survival in selected patients with T4a rectal carcinoma. With optimal treatment local recurrence is a sign of systemic disease.
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Affiliation(s)
- D A Harris
- Abertawe Bro Morgannwg University Local Health Board, Swansea, UK.
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Lawlor G, Moss AC. Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 2010; 16:1620-7. [PMID: 20232408 DOI: 10.1002/ibd.21275] [Citation(s) in RCA: 194] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The role of cytomegalovirus (CMV) in exacerbations of inflammatory bowel disease (IBD) remains a topic of ongoing debate. Current data are conflicting as to whether CMV worsens inflammation in those with severe colitis, or is merely a surrogate marker for severe disease. The interpretation of existing results is limited by mostly small, retrospective studies, with varying definitions of disease severity and CMV disease. CMV colitis is rare in patients with Crohn's disease or mild-moderate ulcerative colitis. In patients with severe and/or steroid-refractory ulcerative colitis, local reactivation of CMV can be detected in actively inflamed colonic tissue in about 30% of cases. Where comparisons between CMV+ and CMV- steroid-refractory patients can be made, most, but not all, studies show no difference in outcomes according to CMV status. Treatment with antiviral therapy has allowed some patients with severe colitis to avoid colectomy despite poor response to conventional IBD therapies. This article reviews the immunobiology of CMV disease, the evidence for CMV's role in disease severity, and discusses the outcomes with antiviral therapy.
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Affiliation(s)
- Garrett Lawlor
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
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Kang MK, Kim MS, Kim JH. Intraoperative radiotherapy for locally advanced rectal cancer. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2010; 26:274-278. [PMID: 21152229 PMCID: PMC2998003 DOI: 10.3393/jksc.2010.26.4.274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2009] [Accepted: 06/07/2010] [Indexed: 11/04/2022]
Abstract
PURPOSE Although intraoperative radiotherapy (IORT) is known to be a method that can reduce local recurrence in locally advanced colorectal cancer, it is not widely used. The aim of this study was to report our experience with IORT for locally advanced rectal cancer. METHODS From 1991 to 1994, nine patients with locally advanced rectal cancer received IORT. External beam radiotherapy was given postoperatively in five patients and preoperatively in three. Seven patients received chemotherapy. IORT was done with 6-MeV or 9-MeV electrons, and 12 Gy was irradiated at the tumor bed. The median follow-up period was 84 months (range, 15 to 208 months). RESULTS The median age of patients was 51 years (range, 42 to 73 years). All patients had advanced clinical T-stage (cT3/4) cancer. The overall and the disease-free survival rates were 66.7% and 66.7% at 5 years, respectively. One patient developed a local recurrence near the anastomosis site, which was out of the IORT field. Four patients died before the last follow-up; three from distant metastasis and one from secondary primary cancer. Adverse effects related to IORT did not occur. CONCLUSION Although the number of patients was small in this study, IORT is thought to be safe and effective in reducing local recurrence in locally advanced rectal cancer. However, the role of IORT should be refined in the era of preoperative radio-chemotherapy followed by total mesorectal excision.
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Affiliation(s)
- Min Kyu Kang
- Department of Radiation Oncology, Yeungnam University College of Medicine, Daegu, Korea
| | - Myung Se Kim
- Department of Radiation Oncology, Yeungnam University College of Medicine, Daegu, Korea
| | - Jae Hwang Kim
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
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Cytomegalovirus infection in patients with active inflammatory bowel disease. Dig Dis Sci 2010; 55:1059-65. [PMID: 20112061 DOI: 10.1007/s10620-010-1126-4] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2009] [Accepted: 01/11/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND The reported prevalence of cytomegalovirus (CMV) infection with active inflammatory bowel disease (IBD) is highly variable, and whether CMV negatively impacts the clinical course is controversial. AIMS The aim of this study was to determine the prevalence of CMV in patients with active ulcerative colitis (UC) or Crohn's disease (CD) and compare the course of disease in patients with and without CMV. METHODS Consecutive patients with acute exacerbations of active IBD colitis had immunohistochemistry staining for CMV antigen performed on archived specimens. Clinical features were retrospectively reviewed. RESULTS Twelve (10%) of 122 UC patients had CMV, and 0/20 patients with CD had CMV. Of 12 UC patients with CMV infection, seven were not taking steroids or immunosuppressives at their index flare. UC patients with CMV were more likely to have leukocytosis (OR = 5.3, 95% CI 1.5-18.2), require hospitalization (OR = 4.9, 95% CI 1.2-19.0), and be hospitalized > or =7 days (OR = 5.0, 95% CI 1.6-21.3) compared to patients without CMV. Of 12 UC patients with CMV, ten (83%) were treated for their index flare with steroids or 6-mercaptopurine. Only one patient (8%) was treated for CMV infection which occurred 14 months after index endoscopy. Over the 6 months after the index flare, UC patients with CMV had a higher frequency of IBD-related hospitalizations compared to patients without CMV (50 vs. 24%, P = 0.021), but none required surgery or died. CONCLUSIONS The prevalence of CMV with active UC was 10%. Although CMV infection may be a marker of disease severity, our results suggest it does not cause severe morbidity or mortality in a general population of patients with a UC flare.
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Maher MM, Nassar MI. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci 2009; 54:2456-62. [PMID: 19093204 DOI: 10.1007/s10620-008-0639-6] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2008] [Accepted: 11/12/2008] [Indexed: 12/12/2022]
Abstract
The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn's diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1+/-0.3 vs. 5.9+/-3.4 and 98+/-34 vs. 165+/-101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.
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Affiliation(s)
- Maha M Maher
- Department of Internal Medicine, Mansoura University, Mansoura, Egypt,
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Sharma S, Gurakar A, Camci C, Jabbour N. Avoiding pitfalls: what an endoscopist should know in liver transplantation--part II. Dig Dis Sci 2009; 54:1386-402. [PMID: 19085103 DOI: 10.1007/s10620-008-0520-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2007] [Accepted: 08/27/2008] [Indexed: 02/07/2023]
Abstract
Over the last decade the number of patients undergoing transplantation has increased. At the same time, effective peri- and postoperative care and better surgical techniques have resulted in greater numbers of recipients achieving long-term survival. Identification and effective management in the form of adequate treatment is essential, since any delay in diagnosis or treatment may result in graft loss or serious threat to patient's life. Various aspects of endoscopic findings that can be commonly encountered among liver transplant recipients are discussed herein. Topics include: persistent and/or recurrent esophageal varices, reflux, Candida or cytomegalovirus (CMV) esophagitis, esophageal neoplasms, posttransplant peptic ulcer, biliary complications, posttransplant lymphoproliferative disorder (PTLD), Kaposi's sarcoma, CMV colitis and inflammatory bowel disease, colonic neoplasms, Clostridium difficile infection, and graft versus host disease (GVHD).
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Affiliation(s)
- Sharad Sharma
- Nazih Zuhdi Transplant Institute, 3300 North West Expressway, Oklahoma City, OK 73112, USA.
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Domènech E, Vega R, Ojanguren I, Hernández A, Garcia-Planella E, Bernal I, Rosinach M, Boix J, Cabré E, Gassull MA. Cytomegalovirus infection in ulcerative colitis: a prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis 2008; 14:1373-9. [PMID: 18452205 DOI: 10.1002/ibd.20498] [Citation(s) in RCA: 168] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection has been reported in ulcerative colitis (UC), especially in severe, steroid-refractory disease. However, its role in steroid-refractoriness remains unknown. Our goals were to evaluate the prevalence of CMV disease in UC, the best diagnostic strategy, and the influence of disease activity and/or treatment in its development. METHODS Prospective, observational study including 114 subjects with active UC requiring intravenous steroids, steroid-refractory UC, inactive UC on mesalamine, inactive UC on azathioprine, and healthy controls. CMV antibodies, pp65-antigenemia, and rectal biopsies for hematoxylin and eosin staining, immunohistochemistry, and CMV-pp67 mRNA were performed. These procedures were repeated after medical treatment only in patients with active UC. CMV disease was defined by the presence of inclusion bodies and/or positive immunohistochemistry in colonic biopsies. RESULTS CMV disease was found in 6 steroid-refractory, CMV-IgG-positive UC patients but not among controls, inactive UC, or steroid-responding UC patients. In 5 out of the 6 patients, CMV disease was diagnosed after 7-10 days on cyclosporine. CONCLUSIONS CMV disease in UC only affects seropositive, steroid-refractory UC patients. Steroid/cyclosporine treatment together with disease activity may predispose to latent colonic CMV reactivation. The impact of antiviral therapy on the clinical outcome of these patients remains to be elucidated.
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Affiliation(s)
- Eugeni Domènech
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain.
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Glynne-Jones R, Wallace M, Livingstone JIL, Meyrick-Thomas J. Complete clinical response after preoperative chemoradiation in rectal cancer: is a "wait and see" policy justified? Dis Colon Rectum 2008; 51:10-9; discussion 19-20. [PMID: 18043968 DOI: 10.1007/s10350-007-9080-8] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2007] [Revised: 05/14/2007] [Accepted: 05/20/2007] [Indexed: 02/06/2023]
Abstract
PURPOSE A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of "waiting to see" and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery. RESULTS In total, 218 Phase I/II or retrospective studies and 28 Phase III trials of preoperative radiotherapy or chemoradiation were identified: 96 percent of trials documented the pathologic complete response, but only 38 trials presented data on the achievement of a complete clinical response/partial clinical response. Only five studies were found in which patients with clinically staged T2/T3 tumors were treated with radiotherapy/chemoradiation and did not routinely proceed to surgery and also reported on the long-term outcome of a "wait and see" policy. DISCUSSION It remains uncertain whether the degree of response to chemoradiation in terms of complete clinical response or pathologic complete response is a useful clinical end point. Studies that include T3 rectal cancer are associated with high local recurrence rates after nonsurgical treatment. Few studies report long-term outcome after achievement of a complete clinical response. CONCLUSIONS The end point of complete clinical response is inconsistently defined and seems insufficiently robust with only partial concordance with pathologic complete response. The rationale of a "wait and see" policy when complete clinical response status is achieved relies on retrospective observations, which are currently insufficient to support this policy except in patients who are recognized to be unfit for or refuse radical surgery.
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Affiliation(s)
- R Glynne-Jones
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.
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Clinicopathologic characteristics of clinically relevant cytomegalovirus infection in inflammatory bowel disease. J Gastroenterol 2007; 42:823-9. [PMID: 17940835 DOI: 10.1007/s00535-007-2103-3] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2007] [Accepted: 08/03/2007] [Indexed: 02/04/2023]
Abstract
BACKGROUND In this study we aimed to identify clinically relevant patterns of cytomegalovirus (CMV) infection in inflammatory bowel disease. METHODS Twenty-two patients with severe ulcerative colitis (UC), 12 with moderate UC, and 16 with Crohn's disease were studied retrospectively. We confirmed CMV infection immunohistochemically. The patients were classified into three groups according to the density of CMV-infected cells. Clinicopathologic features were compared between the groups. RESULTS Dense CMV infection was found only in five patients with severe UC. Scattered CMV infection was found in nine patients with severe UC, three with moderate UC, and one patient with Crohn's disease, and in three controls (normal mucosa from early colorectal cancer specimens). For patients with severe UC, severity of CMV infection tended to correlate with older age and more rapid deterioration, including toxic megacolon and panperitonitis. The dense CMV group took significantly higher final daily doses of steroids before the operation, and showed steroid resistance. The frequency of emergency surgery was higher and postoperative hospital stay was significantly longer in the dense CMV group. No significant differences were observed in sex, disease duration, steroid administration (total amount or duration), or frequencies of other therapies among the three groups. Immunohistochemically, CMV positivity in endothelial cells around the ulcer base was a significant feature in dense CMV infection, compared with scattered CMV infection. CONCLUSIONS Older patients with severe steroid-resistant UC may be at particular risk for CMV infection. Dense CMV infection, especially when it occurs predominantly in endothelial cells, may be a useful marker for clinically relevant CMV infection.
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Szynglarewicz B, Matkowski R, Kasprzak P, Sydor D, Forgacz J, Pudelko M, Kornafel J. Sphincter-preserving R0 total mesorectal excision with resection of internal genitalia combined with pre- or postoperative chemoradiation for T4 rectal cancer in females. World J Gastroenterol 2007; 13:2339-43. [PMID: 17511034 PMCID: PMC4147144 DOI: 10.3748/wjg.v13.i16.2339] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the impact of chemoradiation admi-nistered pre- or postoperatively on prognosis in females following R0 extended resection with sphincter-preserving total mesorectal excision (TME) for locally advanced rectal cancer and to assess the association between chemoradiation and intra- and postoperative variables.
METHODS: Twenty-one females were treated for locally advanced but preoperatively assessed as primarily resectable rectal cancer involving reproductive organs. Anterior resection with TME and excision of internal genitalia was combined with neo- or adjuvant chemoradiation. Two-year disease-free survival analysis was performed with the Kaplan-Meier method and log-rank test. The association between chemoradiation and other variables was evaluated with the Fisher’s exact test and Mann-Whitney test.
RESULTS: Survival rate decreased in anaemic females (51.5% vs 57.4%), in patients older than 60 years (41.8% vs 66.7%) with poorly differentiated cancers (50.0% vs 55.6%) and tumors located ≤ 7 cm from the anal verge (42.9% vs 68.1%) but with the lack of importance. Patients with negative lymph nodes and women chemoradiated preoperatively had significantly favourable prognosis (85.7% vs 35.7%; P = 0.03 and 80.0% vs 27.3%; P = 0.01, respectively). Preoperative chemoradiation compared to adjuvant radiochemotherapy was not significantly associated with the duration of surgery, incidence of intraoperative bowel perforation and blood loss ≥ 1 L, rate of postoperative bladder and anorectal dysfunction, and minimal distal resection margin. It significantly influenced minimal radial margin (mean 4.2 mm vs 1.1 mm; P < 0.01).
CONCLUSION: Despite involving internal genitalia, long-term disease-free survival and sphincter preservation may be achieved with combined-modality therapy for females with T4 locally advanced rectal carcinoma. Neoadjuvant chemoradiation does not compromise functional results and may significantly improve oncological outcomes probably due to enhanced radial clearance.
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Affiliation(s)
- Bartlomiej Szynglarewicz
- 2nd Department of Surgical Oncology, Lower Silesian Oncology Center-Regional Comprehensive Cancer Center, and Department of Gynaecological Oncology, Wroclaw Medical University, Poland.
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Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, Okamoto S, Morohoshi Y, Izumiya M, Ichikawa H, Sato T, Inoue N, Ogata H, Hibi T. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 2007; 102:331-7. [PMID: 17156136 DOI: 10.1111/j.1572-0241.2006.00989.x] [Citation(s) in RCA: 165] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The clinical significance of cytomegalovirus (CMV) reactivation complicating ulcerative colitis (UC) patients has been uncertain. It has therefore remained undetermined whether or not CMV reactivation should be treated in UC patients under immunosuppression. The aim of the study was to clarify the natural history of CMV reactivation in UC patients. METHODS Sixty-nine UC patients with moderate to severe activity were enrolled in the study. All of the patients were treated with prednisolone, and/or immunosuppressants such as cyclosporine A. We sequentially monitored CMV reactivation every 2 wk up until 8 wk using the CMV antigenemia (Ag) assay and plasma quantitative real-time polymerase chain reaction (PCR) assay for CMV. RESULTS Immunoglobulin (Ig) G for CMV was positive in 48 patients (69.6%) and negative in 21 patients (30.4%). CMV was reactivated in 25 patients out of the 48 seropositive patients (52.1%) during the study period. The CMV Ag and PCR values were low and none of the patients showed any evidence of CMV infection on biopsy specimens by hematoxylin and eosin staining. While gancylovir (GCV) was not used except in two patients, clinical outcomes including rates of remission and colectomy were not significantly different among the CMV reactivation-positive, -negative, and CMV IgG negative groups. Furthermore, CMV disappeared without GCV in most of the CMV reactivation-positive patients. CONCLUSIONS CMV is frequently reactivated in active UC patients; however, it disappears without antiviral agents. Therefore, antiviral therapies should not be necessary for most UC patients with only CMV reactivation as long as CMV Ag values are low.
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Affiliation(s)
- Katsuyoshi Matsuoka
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
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Liszka L, Zielińska-Pajak E, Pajak J, Gołka D, Starzewski J, Lorenc Z. Usefulness of two independent histopathological classifications of tumor regression in patients with rectal cancer submitted to hyperfractionated pre-operative radiotherapy. World J Gastroenterol 2007; 13:515-24. [PMID: 17278216 PMCID: PMC4065972 DOI: 10.3748/wjg.v13.i4.524] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy.
METHODS: Forty patients at the initial stage cT3NxM0 submitted to preoperative radiotherapy (42 Gy during 18 d) and then to radical surgical treatment. The relationship between “T-downstaging” versus regressive changes expressed by tumor regression grade (TRG 1-5) and Nasierowska-Guttmejer classification (NG 1-3) was studied as well as the relationship between TRG and NG versus local tumor stage ypT and lymph nodes status, ypN.
RESULTS: Complete regression (ypT0, TRG 1) was found in one patient. “T-downstaging” was observed in 11 (27.5%) patients. There was a weak statistical significance of the relationship between “T-downstaging” and TRG staging and NG stage. Patients with ypT1 were diagnosed as TRG 2-3 while those with ypT3 as TRG5. No lymph node metastases were found in patients with TRG 1-2. None of the patients without lymph node metastases were diagnosed as TRG 5. Patients in the ypT1 stage were NG 1-2. No lymph node metastases were found in NG 1. There was a significant correlation between TRG and NG.
CONCLUSION: Histopathological classifications may be useful in the monitoring of the effects of hyperfractionated preoperative radiotherapy in patients with rectal cancer at the stage of cT3NxM0. There is no unequivocal relationship between “T-downstaging” and TRG and NG. There is some concordance in the assessment of lymph node status with ypT, TRG and NG. TRG and NG are of limited value for the risk assessment of the lymph node involvement.
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Affiliation(s)
- Lukasz Liszka
- Department of Pathology, Medical University of Silesia, ul. Medykow 14, Katowice 40-754, Poland
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Sasapu KK, Sebag-Montefiore D, Chalmers AG, Sagar PM, Burke D, Finan PJ. Evaluation of a protocol-based management of rectal cancer. Dis Colon Rectum 2006; 49:1703-9. [PMID: 17028915 DOI: 10.1007/s10350-006-0682-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The management of rectal cancer is multidisciplinary. We have devised and implemented a standardized protocol. This study was designed to evaluate the protocol and identify areas for improvement. METHODS All patients with a diagnosis of rectal cancer were staged preoperatively. Magnetic resonance imaging and computed tomography were used to predict whether surgical resection would be complete (RO) or involved (R1/2). Data were collected on preoperative adjuvant therapy, surgical procedure, and subsequent pathologic stage, including circumferential resection margin status. RESULTS Between January 2000 and October 2002, 163 patients were studied (107 male; median age, 70 (range, 60-77) years). One hundred and fifty seven patients underwent surgical excision for rectal cancer of whom 155 were discussed in the multidisciplinary meeting. One hundred seventeen patients (75 percent) had pelvic magnetic resonance scan and staging computed tomography of chest and abdomen, whereas 38 had computed tomography only. Seventy-seven tumors were predicted as R0 and 78 as likely R1/2. In the predicted RO group, 50 had surgery alone, 25 had short-course radiotherapy, and 2 had chemoradiotherapy. Twelve patients (15.5 percent) had involved circumferential resection margin on the histologic specimen. In the predicted R1/2 group (n = 78), 40 patients received chemoradiotherapy, 11 had short-course radiotherapy, and 27 had surgery alone. Thirty patients (38.4 percent) had involved circumferential resection margin. Circumferential margin involvement was seen in 11 of 40 patients (27.5 percent) who received chemoradiotherapy, 6 of 11 patients (54.5 percent) who received short-course preoperative radiotherapy, and 13 of 27 patients (48.1 percent) who had surgery alone. CONCLUSIONS Protocol-driven management of rectal cancer within the context of a multidisciplinary team has been demonstrated to work. Regular audit allows for modification and improvement of the protocol as newer management strategies evolve.
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Affiliation(s)
- Kishore K Sasapu
- Department of Colorectal Surgery, The General Infirmary at Leeds, Leeds, West Yorkshire, United Kingdom
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Krempien R, Roeder F, Oertel S, Roebel M, Weitz J, Hensley FW, Timke C, Funk A, Bischof M, Zabel-Du Bois A, Niethammer AG, Eble MJ, Buchler MW, Treiber M, Debus J. Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2006; 66:1143-51. [PMID: 16979835 DOI: 10.1016/j.ijrobp.2006.06.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2006] [Revised: 06/02/2006] [Accepted: 06/15/2006] [Indexed: 11/23/2022]
Abstract
BACKGROUND We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.
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Affiliation(s)
- Robert Krempien
- Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
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Calvo FA, Meirino RM, Orecchia R. intraoperative radiation therapy part 2. Clinical results. Crit Rev Oncol Hematol 2006; 59:116-27. [PMID: 16859922 DOI: 10.1016/j.critrevonc.2006.04.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2005] [Revised: 03/30/2006] [Accepted: 04/13/2006] [Indexed: 12/12/2022] Open
Abstract
Intraoperative radiation therapy (IORT) has been used for over 30 years in Asia, Europe and America as a supplementary activity in the treatment of cancer patients with promising results. Modern IORT is carried out with electron beams (IOERT) produced by a linear accelerator generally used for external beam irradiation (EBRT) or a specialized mobile electron accelerator. HDR brachytherapy (HDR-IORT) has also been applied on selected locations. Retrospective analysis of clinical experiences in cancer sites such as operable pancreatic tumour, locally advanced/recurrent rectal cancer, head and neck carcinomas, sarcomas and cervical cancer are consistent with local tumour control promotion compared to similar clinical experiences without IORT. New emerging indications such as the treatment of breast cancer are presented. The IORT component of the therapeutical approach allows intensification of the total radiation dose without additional exposure of healthy tissues and improves dose-deposit homogeneity and precision. Results of the application of IORT on selected disease sites are presented with an analysis on future possibilities. To improve the methodology, clinical trials are required with multivariate analysis including patient, tumour and treatment characteristics, prospective evaluation of early and late toxicity, patterns of tumour recurrence and overall patient outcome.
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Affiliation(s)
- Felipe A Calvo
- Hospital General Universitario Gregorio Marañon, Madrid, Spain.
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43
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Kou T, Nakase H, Tamaki H, Kudo T, Nishio A, Chiba T. Cytomegalovirus infection in patients with ulcerative colitis diagnosed by quantitative real-time PCR analysis. Dig Dis Sci 2006; 51:1052-5. [PMID: 16865568 DOI: 10.1007/s10620-006-8006-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2005] [Accepted: 07/27/2005] [Indexed: 12/13/2022]
Affiliation(s)
- Tadayuki Kou
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin, Kyoto, 606-8507, Japan
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44
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Kojima T, Watanabe T, Hata K, Shinozaki M, Yokoyama T, Nagawa H. Cytomegalovirus infection in ulcerative colitis. Scand J Gastroenterol 2006; 41:706-11. [PMID: 16716970 DOI: 10.1080/00365520500408584] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Cytomegalovirus (CMV) infection has been reported as an exacerbating factor in inflammatory bowel disease but the relationship between CMV infection and ulcerative colitis (UC) remains unclear. There has been no detailed research to elucidate the clinicopathologic features of CMV infection in UC using surgical specimens. The aim of this study was to investigate the clinicopathologic features of CMV infection in UC patients who had undergone colectomy. MATERIAL AND METHODS Surgical specimens taken from UC patients were examined for CMV infection. The patients were divided into three groups: severe, refractory, and UC-associated dysplasia or cancer according to the operative indications. CMV infection rates were evaluated and a comparison of clinical parameters was made between CMV-positive and CMV-negative patients, and the risk factors for CMV infection were analyzed using multivariate analyses. RESULTS It was found that 25% of 32 patients were positive for CMV in the severe UC group; 8.3% of 72 patients were positive for CMV in the refractory UC group. None of the 22 patients was positive for CMV in the UC-associated dysplasia or cancer group. The CMV-positive rate in the severe UC group was significantly higher than that in the other groups (p<0.05). Patients' age at the time of operation was higher in the CMV-positive group than in the CMV-negative group among the patients with severe UC (p<0.01), and age at operation was an independent risk factor for CMV infection. CONCLUSIONS CMV is found more frequently in severe UC than refractory UC and UC-associated cancer or dysplasia. Higher age can be a risk factor for CMV infection in patients with severe UC. However, a high steroid dose may not always be a risk factor for CMV infection.
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Affiliation(s)
- Tetsu Kojima
- Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
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Howell DD. The role of radiation therapy in the palliation of gastrointestinal malignancies. Gastroenterol Clin North Am 2006; 35:125-30. [PMID: 16530115 DOI: 10.1016/j.gtc.2005.12.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Radiation therapy can provide significant palliation in many patients who have unresectable, metastatic, or incurable malignancies of the gastrointestinal tract and is a modality that can be used in many clinical situations. In considering radiation therapy, the radiation oncologist should be mindful of the actual expectation of palliation, the potential degree of relief of symptoms, and the time involved for the patient and those involved in his or her care and transport. When a course of radiation is planned, the dose per fraction, total number of fractions, and total dose delivered should all be taken into account. The use of concurrent systemic chemotherapy needs to be reviewed with respect to chances for augmentation of palliation as well as morbidity. Although long-term disease control is often not achieved, there are reasonable expectations for control of symptoms of bleeding and pain. The side effects associated with radiation are generally well tolerated and, if they occur, usually can be controlled with conservative measures. Significant late effects, although uncommon, are generally a function of the volume of the organ treated, the total dose used, and whether systemic therapy is used in conjunction with radiation. When considering the options for palliation in these situations, multidisciplinary collaboration among all those involved in a patient's care, surgeon, radiation oncologist, medical oncologist, primary care provider, and palliative care specialist, is ideal to address each situation in each patient, for whom there may be a variety of options for palliative treatment. Generally, combinations of interventions are needed to optimize the palliation of a patient's various problems. The goal of providing relief to the patient in the least amount of time with the least amount of morbidity and the greatest expectation for durability of response is paramount.
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Affiliation(s)
- David D Howell
- Department of Radiation Oncology, University of Michigan School of Medicine, UH B2C 490 UH 0010, Ann Arbor 48109, USA.
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46
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Kugathasan S, Dubinsky MC, Keljo D, Moyer MS, Rufo PA, Wyllie R, Zachos M, Hyams J. Severe colitis in children. J Pediatr Gastroenterol Nutr 2005; 41:375-85. [PMID: 16205502 DOI: 10.1097/01.mpg.0000186272.65559.ce] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Subra Kugathasan
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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Palmer G, Martling A, Blomqvist L, Cedermark B, Holm T. Outcome after the introduction of a multimodality treatment program for locally advanced rectal cancer. Eur J Surg Oncol 2005; 31:727-34. [PMID: 15979271 DOI: 10.1016/j.ejso.2005.04.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2005] [Revised: 04/04/2005] [Accepted: 04/22/2005] [Indexed: 11/24/2022] Open
Abstract
AIM This prospective study reports the results of a multimodality treatment protocol in patients with locally advanced rectal cancer and assesses outcome after curative vs non-curative surgery and in relation to primary advanced vs locally recurrent cancer. METHODS Between 1991 and 2002, 122 patients completed the protocol. Fifty-eight had primary advanced and sixty-four had locally recurrent rectal cancer. Median follow up was 82 months (5-143). RESULTS A potentially curative resection was achieved in 59% of the patients with primary advanced and in 34% of patients with locally recurrent cancer. After curative resection, 53 and 59%, respectively, were free from recurrence during the observation time (median 82 months) and the overall 5-year survival was 34 and 40%. Overall 5-year survival in all patients with primary advanced cancer was 29 and 16% in all patients with locally recurrent rectal cancer. CONCLUSION Multimodality treatment may cure at least a third of patients with locally advanced rectal cancer provided a radical resection is performed. As the post-operative morbidity is high, an optimised patient selection for neo-adjuvant treatment and surgery is essential. However, palliative surgery may benefit the patient if local control is achieved. Future studies should focus on the problem of distant metastasis.
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Affiliation(s)
- G Palmer
- Department of Surgery, Karolinska University Hospital and Karolinska Institute, SE-171 76 Stockholm, Sweden.
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Ratto C, Grillo E, Parello A, Petrolino M, Costamagna G, Doglietto GB. Sacral neuromodulation in treatment of fecal incontinence following anterior resection and chemoradiation for rectal cancer. Dis Colon Rectum 2005; 48:1027-36. [PMID: 15785890 DOI: 10.1007/s10350-004-0884-5] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Fecal incontinence may occur in patients who have undergone anterior resection for rectal cancer without presenting sphincter lesions. Chemoradiation may contribute to disrupting continence mechanisms. Treatment is controversial. Assessment of fecal incontinence in patients who agreed to integrate treatment for rectal cancer and treatment with sacral neuromodulation are reported. METHODS Fecal incontinence following preoperative chemoradiation and anterior resection for rectal cancer was evaluated in four patients. A good response was observed during the percutaneous sacral nerve evaluation test, and so permanent implant of sacral neuromodulation system was performed. Reevaluation was performed at least two months after implant. RESULTS After device implantation, the mean fecal incontinence scores decreased, and the mean number of incontinence episodes dropped from 12.0 to 2.5 per week (P < 0.05). Permanent implant resulted in a significant improvement in fecal continence in three patients, and incontinence was slightly reduced in the fourth. Manometric parameters agreed with clinical results: maximum and mean resting tone and the squeeze pressure were normal in three patients and reduced in one. In these same three patients, neorectal sensation parameters increased when the preoperative value was normal or below normal and decreased when the preoperative value was higher than normal, whereas in one patient in whom extremely low values were recorded all of the parameters decreased significantly. CONCLUSIONS Fecal incontinence following anterior resection and neoadjuvant therapy should be carefully evaluated. If a suspected neurogenic pathogenesis is confirmed, sacral neuromodulation may be proposed. If the test results are positive, permanent implant is advisable. Failure of this approach does not exclude the use of other, more aggressive treatment.
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Affiliation(s)
- Carlo Ratto
- Department of Clinica Chirurgica, Catholic University, 00168 Rome, Italy.
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Zmora O, Dasilva GM, Gurland B, Pfeffer R, Koller M, Nogueras JJ, Wexner SD. Does rectal wall tumor eradication with preoperative chemoradiation permit a change in the operative strategy? Dis Colon Rectum 2004; 47:1607-12. [PMID: 15540288 DOI: 10.1007/s10350-004-0673-1] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Preoperative chemoradiation may downstage locally advanced rectal cancer and, in some cases, with no residual tumor. The management of complete response is controversial and recent data suggest that radical surgery may be avoided in selected cases. Transanal excision of the scar may determine the rectal wall response to chemoradiation. This study was designed to assess whether the absence of tumor in the bowel wall corresponds to the absence of tumor in the mesorectum, known as true complete response. METHODS A retrospective review of the medical records of patients who underwent preoperative chemoradiation for advanced mid (6-11 cm from the anal verge) and low (from the dentate line to 5 cm from the anal verge) rectal cancer (uT2-uT3) followed by radical surgery with total mesorectal excision was undertaken. Patients in whom the pathology specimen showed no residual tumor in the rectal wall (yT0, "y" signifies pathologic staging in postradiation patients) were assessed for tumoral involvement of the mesorectum. RESULTS A total of 109 patients underwent preoperative, high-dose radiation therapy (94 percent with 5-fluorouracil chemosensitization), followed by radical surgery for advanced rectal cancer. Preoperatively, 47 patients were clinically assessed to have potentially complete response. After radical rectal resection, pathology did not reveal any residual tumor within the rectal wall (yT0) in 17 patients. In two (12 percent) of these patients, the mesorectum was found to be positive for malignancy: one had positive lymph nodes that harbored cancer; one had tumor deposits in the mesorectal tissue. CONCLUSIONS Compete rectal wall tumor eradication does not necessarily imply complete response, because the mesorectum may harbor tumor cells. Thus, caution should be exercised when considering the avoidance of radical surgery. Reliable imaging methods and clinical predictors for favorable outcome are important to allow less radical approaches in the future.
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Affiliation(s)
- Oded Zmora
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA
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Klaassen RA, Nieuwenhuijzen GAP, Martijn H, Rutten HJT, Hospers GAP, Wiggers T. Treatment of locally advanced rectal cancer. Surg Oncol 2004; 13:137-47. [PMID: 15572096 DOI: 10.1016/j.suronc.2004.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Historically, locally advanced rectal cancer is known for its dismal prognosis. The treatment of locally advanced rectal cancer is subject to continuous change due to development of new and better diagnostic tools, radiotherapeutic techniques, chemotherapeutic agents and understanding of the subject. It is clear, that a multimodality approach is the only way to achieve satisfactory local recurrence and survival rates in this type of cancer. However, which multimodality strategy is to be used still remains a point of controversy. This review summarises recent developments in imaging, (neo-) adjuvant therapy and surgical techniques in the treatment of primary locally advanced rectal cancer.
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Affiliation(s)
- René A Klaassen
- Department of Surgery, Catharina Hospital Eindhoven, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands
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