No-touch isolation technique reduces intraoperative shedding of tumor cells into the portal vein during resection of colorectal cancer

doi:10.1016/S0039-6060(99)70003-6

Surgery

Volume 125, Issue 4, April 1999, Pages 369-374

https://doi.org/10.1016/S0039-6060(99)70003-6 Get rights and content

Abstract

Background: The mutant-allele–specific amplification (MASA) method is capable of detecting 1 genetically altered tumor cell among thousands of normal cells. The MASA enabled us to detect occult tumor cells undetectable by histopathologic examination of lymph nodes and blood samples. Methods: To investigate whether tumor manipulation during operation enhances cancer cell dissemination into the portal vein with use of MASA and to assess the effect of the no-touch isolation technique in the treatment of colorectal cancers, 27 colorectal cancers (17 were operated on conventionally and 10 were operated on according to the no-touch isolation technique) were screened for mutations in K-ras or p53. We next examined blood samples of the portal vein collected before, during, and after manipulation of tumors, using MASA to look for the specific mutation found in the primary tumors. Results: Somatic mutations were identified in 18 of these primary tumors (11 were in the conventional resection technique group and 7 were in the no-touch isolation technique group). In 8 of 11 (73%) conventional resection technique cases, we identified the same genetic alteration of the primary tumor in the portal blood during operation, whereas only 1 patient (14%) in the no-touch isolation technique group had a positive result. Conclusions: The no-touch isolation technique may be useful to prevent cancer cells from being shed into the portal vein during surgical manipulation. (Surgery 1999;125:369-74.)

Section snippets

Patients

All patients were thoroughly informed about the study and gave written consent for investigation in accordance with the ethical guidelines of our university. Twenty-seven patients with colorectal cancer who underwent surgery at the Department of Surgery II, Kumamoto University Hospital, or at the Department of Surgery, Kumamoto Central Hospital, Kumamoto, Japan, were included in our study. Conventional operation was performed in 17 cases: cecal lesions (n = 3), ascending colon (n = 1),

Results

We initially performed the conventional method as a standard operation for patients with colorectal cancer. Seventeen patients who underwent operation by the conventional method were studied to examine tumor cell dissemination into the portal vein by manipulation during operation. In each of the primary tumors we looked for somatic mutations in selected regions of the K-ras or p53 genes. We used MASA⁹ to examine mutations at codons 12, 13, and 61 of K-ras . PCR reactions with MASA primers that

Discussion

Hematogenous spread of tumor cells seems to influence the outcome of the disease for most cancer patients. However, little is known about the nature of this process. Because the number of tumor cells in blood is very small, techniques for their detection need to be not only highly sensitive but also specific.

The advent of PCR has made an enormous impact on nucleic acid analysis.¹⁵ PCR-based techniques have improved the sensitivity of detection systems for disseminated tumor cells. Reverse

Acknowledgements

We thank the physicians in the Department of Surgery II, Kumamoto University Medical School, Kumamoto, and the Department of Surgery, Kumamoto Central Hospital, Kumamoto, for providing appropriate tissue samples.

References (23)

J Ovaska et al.
Follow-up of patients operated on for colorectal carcinoma
Am J Surg
(1990)
T Nishizaki et al.
Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis
J Surg Res
(1990)
B Smith et al.
Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction
Lancet
(1991)
N Hayashi et al.
Genetic diagnosis of lymph-node metastasis in colorectal cancer
Lancet
(1995)
H Naito et al.
Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by reverse transcription–polymerase chain reaction
Eur J Cancer
(1991)
DC Brown et al.
Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction
Surgery
(1995)
GA Kune et al.
Survival in patients with large-bowel cancer
Dis Colon Rectum
(1990)
JP Barnes
Physiologic resection of the right colon
Surg Gynecol Obstet
(1952)
RB Turnbull et al.
Cancer of the colon: the influence of the no-touch isolation technic on survival rates
Ann Surg
(1967)
T Wiggers et al.
No-touch isolation technique in colon cancer: a controlled prospective trial
Br J Surg
(1988)

P Johnson et al.

The molecular detection of circulating tumor cells

Br J Cancer

(1995)

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Liquid biopsy after resection of pancreatic adenocarcinoma and its relation to oncological outcomes. Systematic review and meta-analysis
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It has been hypothesised that manipulation during surgery releases tumoral components into circulation. We investigate the effect of surgery on plasma-borne DNA biomarkers and the oncological outcomes in resectable pancreatic ductal adenocarcinoma (PDAC). We also compare non-touch isolation techniques (NTIT) with standard techniques.
We performed a systematic review and a meta-analysis of studies analysing liquid biopsy as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and messenger RNA (mRNA) in resectable PDAC patients who underwent surgery and its association with overall survival (OS) and disease-free survival (DFS). Research in EMBASE, Web of Science and PubMed was performed. The ctDNA shift negative-to-positive (ctDNA −/+) or ctDNA shift positive-to-negative (ctDNA +/−) before and after surgery was evaluated.
Twelve studies comprising 413 patients were included. Shorter OS and DFS were identified in patients with positive ctDNA status before (HR = 2.28, p = 0.005 and HR = 2.16, p = 0.006) or after surgery (HR = 3.88, p < 0.0001 and HR = 3.81, p = 0.03), respectively. Surgical resection increased the rate of ctDNA +/−. There were no differences in OS or DFS in the ctDNA +/− group compared with ctDNA +/+ or ctDNA −/+. However, there was a trend to shorter OS in the ctDNA −/+ group (HR = 5.00, p = 0.09). No differences between NTIT and standard techniques on liquid biopsy status were found.
Positive ctDNA in the perioperative period is associated with a worse prognosis. Surgical resection has a role in the negativisation of liquid biopsy status. More studies are needed to assess the potential of minimally invasive techniques on ctDNA dynamics.
Influence of the no-touch isolation technique on oncologic outcomes for patients with colon cancer undergoing curative surgery: A systematic review and meta-analysis
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To explore the influence of the no-touch isolation technique (NTIT) on oncologic outcomes for patients with colon cancer (CC) undergoing curative surgery.
Although several studies have investigated this topic, there have been no meta-analyses exploring the influence of NTIT on oncologic outcomes for these patients.
We performed a comprehensive electronic literature search of studies published prior to March 2022 to identify those that compared oncologic outcomes for patients with CC who did or did not undergo NTIT. We conducted a meta-analysis using a random-effects model to calculate risk ratio (RRs) and 95% confidence intervals (CIs), analyzing heterogeneity using I² statistics.
Four studies involving a total of 2885 patients with CC who underwent curative surgery met the inclusion criteria for this meta-analysis. The 5-year overall survival (OS) rate was 76.6% for patients with CC who underwent NTIT and 77.2% for those who did not. A meta-analysis of the 3 studies that reported 5-year OS revealed no significant difference between groups (RR, 0.84; 95% CI, 0.62–1.16; P = 0.30; I² = 70%). In addition, there were no significant differences in 5-year recurrence-free survival (RR, 1.17; 95% CI, 0.93–1.48; P = 0.19; I² = 45%), and 5-year liver recurrence-free survival (RR, 0.95; 95% CI 0.62, 1.46; P = 0.82; I² = 65%).
The use of NTIT has no significant influence on oncologic outcomes for patients with CC undergoing curative surgery.
The “No-touch” technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial
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Citation Excerpt :
Improvements in the operation technique mean improvements in the LT standard. Better results using the no-touch technique have been clearly demonstrated in other studies [19,20,22,31]. Therefore, no-touch LT may become a new paradigm in the treatment of patients with advanced HCC.
Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the “no-touch” technique in LT.
From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed.
The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than those in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024).
The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.
Prophylactic hyperthermic intraperitoneal chemotherapy for patients with clinical T4 gastric cancer
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Patients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer.
We retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups.
A total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group.
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The relevance of liquid biopsy in surgical oncology: The application of perioperative circulating nucleic acid dynamics in improving patient outcomes
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Liquid biopsy is gaining increasing clinical utility in the management of cancer patients. The main components of a liquid biopsy are circulating nucleic acids, circulating tumour cells and extracellular vesicles such as exosomes. Circulating nucleic acids including cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) in particular have been the focus of recent attention as they have demonstrated excellent potential in cancer screening, provision of prognostic information and in genomic profiling of a tumour without the need for repeated tissue biopsies. The aim of this review was to explore the current evidence in relation to the use of liquid biopsy in the perioperative setting and identify ways in which liquid biopsy may be applied in the future.
This narrative review is based on a comprehensive literature search up to the 1st of June 2020 for papers relevant to the application of liquid biopsy in surgical oncology, focusing particularly on the perioperative period.
Recent evidence has demonstrated that perioperative liquid biopsy can accurately stratify patients’ risk of recurrence compared to conventional biomarkers. Attention to the perioperative dynamics of liquid biopsy components can potentially provide new understanding of the complex relationship between surgery and cancer outcome. In addition, careful evaluation of liquid biopsy components in the perioperative window may provide important diagnostic and therapeutic information for cancer patients.
The rapidly evolving concept of the liquid biopsy has the potential to become the cornerstone for decision making around surveillance and adjuvant therapies the era of personalised medicine.
The sequence of pulmonary vessels ligation during lobectomy for non-small cell lung cancer: A systematic review and meta-analysis
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The effects of ligating the pulmonary vein first or pulmonary artery first during lobectomy on the long-term survival of patients with non-small cell lung cancer (NSCLC) remain controversial. We conducted the first systematic review and meta-analysis to determine the association between different sequences of vessel ligation during lobectomy and the prognosis of patients with NSCLC.
Literature retrieval was performed by systematically searching Embase, PubMed and Web of Science to identify relevant articles published from the inception of each database to November 2020. The overall survival (OS) and disease-free survival (DFS) of patients treated with vein-first ligation versus those treated with artery-first ligation during lobectomy were analyzed. A standard fixed-effect model test (Mantel-Haenszel method) was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the Q-test and I²-test. Sensitivity analysis was performed to further examine the stability of pooled HRs.
Five studies with a total of 1109 patients receiving lobectomy, including one randomized controlled trial and four retrospective studies, were included in this meta-analysis. The results showed that patients with vein-first ligation had a significantly better OS (HR 1.25, 95% CI 1.03–1.50; P = 0.02) and DFS (HR 1.54, 95% CI 1.16–2.04; P = 0.003) than those with artery-first ligation during lobectomy. Significant heterogeneity and publication bias were not observed during analysis.
Our meta-analysis indicates that vein-first ligation may improve the prognosis of NSCLC patients receiving lobectomy. Therefore, vein-first ligation is recommended during lobectomy for patients with non-small cell lung cancer whenever possible.

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^☆: Supported in part by a Grant-in Aid from the Ministry of Education, Culture, and Science of Japan and by a grant from the Japanese Society for Advancement of Surgical Technique.

^☆☆: Reprint requests: Michio Ogawa, MD, PhD, Department of Surgery II, Kumamoto University Medical School, Honjo 1-1-1, Kumamoto 860-0811, Japan.

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Original CommunicationsNo-touch isolation technique reduces intraoperative shedding of tumor cells into the portal vein during resection of colorectal cancer☆,☆☆

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

Am J Surg

J Surg Res

Lancet

Lancet

Eur J Cancer

Surgery

Survival in patients with large-bowel cancer

Dis Colon Rectum

Physiologic resection of the right colon

Surg Gynecol Obstet

Cancer of the colon: the influence of the no-touch isolation technic on survival rates

Ann Surg

No-touch isolation technique in colon cancer: a controlled prospective trial

Br J Surg

The molecular detection of circulating tumor cells

Br J Cancer

Original Communications
No-touch isolation technique reduces intraoperative shedding of tumor cells into the portal vein during resection of colorectal cancer☆,☆☆