Diagnostic value of FDG-PET/CT for lateral pelvic lymph node metastasis in rectal cancer treated with preoperative chemoradiotherapy

Background

The aim of this study was to elucidate the diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (PET)–computed tomography (CT) for lateral pelvic lymph node (LPN) metastasis in rectal cancer treated with preoperative chemoradiotherapy (CRT).

Methods

Eighteen rectal cancer patients with enlarged (≥?8 mm) LPNs were treated with CRT followed by total mesorectal excision with LPN dissection during 2012–2015. After CRT, LPN maximum standard uptake values (SUVmax) were measured using PET/CT and long diameters of LPNs were measured using CT or magnetic resonance imaging (MRI). LPN size and SUVmax were compared with pathological status in the resected specimen. Radiologically identified nodes were matched with surgically resected nodes by separate examination of 4 lymph nodal regions: internal iliac, obturator, external iliac and common iliac lymph nodes.

Results

In total, 34 LPNs were located by CT or MRI. Metastatic LPNs were significantly larger than non-metastatic LPNs (size, mean?±?standard deviation: 13.0?±?8.3 vs. 4.9?±?3.5 mm, p?<?0.01). SUVmax was determinable for 28 of the LPNs, among which metastatic LPNs were found to have significantly higher SUVmax than non-metastatic LPNs (mean?±?standard deviation: 2.2?±?1.3 vs. 1.2?±?0.3, p?<?0.01). Receiver operating characteristic analysis suggested optimal cutoff values of size?=?12 mm which had an accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 82.1, 70.6, 100, 100, and 68.8%, respectively. An SUVmax?=?1.6 had an accuracy, sensitivity, specificity, PPV, and NPV of 85.7, 76.5, 100, 100, and 73.3%, respectively. When LPNs that were?≥?12 mm in size and/or had an SUV?≥?1.6, the accuracy, sensitivity, specificity, PPV, and NPV were 92.9, 88.2, 100, 100, and 84.6%, respectively.

Conclusions

After CRT, PET/CT alone or in combination with CT and MRI can predict the presence of metastatic LPN with a high degree of accuracy. PET/CT may be useful in selecting patients with rectal cancer who would benefit from LPN dissection in addition to TME. These results need to be confirmed by larger studies.

     

Prognostic value of lateral lymph node metastasis for advanced low rectal cancer

AIM： To evaluate the risk factors for lateral lymph node metastasis in patients with advanced low rectal cancer, in order to make the effective selection of patients who could benefit from lateral lymph node dissection, as well as the relationship of lateral lymph node metastasis with local recurrence and survival of patients with advanced low rectal cancer. METHODS： A total of 96 consecutive patients who underwent curative surgery with lateral pelvic lymphadenectomy for advanced lower rectal cancer were retrospectively analyzed. The relation of lateral lymph node metastasis with clinicopathologic characteristics, local recurrence and survival of patients was identified. RESULTS： Lateral lymph node metastasis was observed in 14.6% （14/96） of patients with advanced low rectal cancer. Lateral lymph node metastasis was detected in 10 （25.0%） of 40 patients with tumor diameter ≥ 5 cm and in 4 （7.1%） of 56 patients with tumor diameter 〈 5 cm. The difference between the significant （X^2 = 5.973, P = two groups was statistically 0.015）. Lateral lymph node metastasis was more frequent in patients with 4/4 diameter of tumor infiltration （7 of 10 cases, 70.0%）, compared with patients with 3/4, 2/4 and 1/4 diameter of tumor infiltration （3 of 25 cases, 12.0%; 3 of 45 cases, 6.7%; 1 of 16 cases, 6.3%） （X^2 = 27.944, P = 0.0001）. The lateral lymph node metastasis rate was 30.0% （9 of 30 cases）, 9.1% （4 of 44 cases） and 4.5% （1 of 22cases） for poorly, moderately and well-differentiated carcinoma, respectively. The difference between the three groups was statistically significant （X^2 = 8.569, P = 0.014）. Local recurrence was 18.8% （18 of 96 cases）, 64.3% （9 of 14 cases）, and 11.0% （9 of 82 cases） in patients with advanced low rectal cancer, in those with and without lateral lymph node metastasis, respectively. The difference between the two groups was statistically significant （X^2 = 22.308, P = 0.0001）. Kaplan-Meier survival analysis showed significant impr     

Risk factors of lateral pelvic lymph node metastasis in advanced rectal cancer

Background  To clarify the risk factors of lateral pelvic lymph node (LPLN) metastasis of rectal cancer, we examined associations between LPLN status and clinicopathological factors including LPLN status diagnosed by computed tomography (CT). Methods  We reviewed a total of 210 patients with advanced rectal cancer, of which the lower margin was located at or below the peritoneal reflection, who underwent preoperative CT with 5-mm-thick sections and lateral pelvic lymph node dissection at the National Cancer Center Hospital between February 1998 and March 2006. Results  Forty-seven patients (22.4%) had LPLN metastasis. Multivariate analysis showed that LPLN status diagnosed by CT, pathological regional lymph node status, tumor location, and tumor differentiation were significant risk factors for LPLN metastasis. Among 45 patients with well-differentiated adenocarcinoma who were LPLN-negative and in whom CT had found no regional lymph node metastasis, none had LPLN metastasis. On the other hand, among 13 patients with moderate or less differentiated lower rectal adenocarcinoma who were LPLN-positive and in whom CT had revealed regional lymph node metastasis, 12 (92.3%) had LPLN metastasis. Conclusions  LPLN status diagnosed by CT, pathological regional LN status, tumor location, and tumor differentiation are significant risk factors for LPLN metastasis. Using these factors, patients can be classified as having a low or high risk of LPLN metastasis.     

Lateral lymph node dissection for lower rectal cancer

BACKGROUND/AIMS: This study was conducted to evaluate the effects of lateral lymph node dissection (LLD) on overall survival, disease-free survival, and local recurrence for the patients with lower rectal cancer. METHODOLOGY: From 1990 through 2000, 169 consecutive patients with T2 (TNM classification) or more advanced, extended lower rectal cancer (located below the peritoneal reflection) underwent curative resection at Kanagawa Cancer Center were reviewed. One hundred and forty-three patients who underwent LLD and the 26 patients who did not were entered in this study. RESULTS: Cox's multivariate regression analysis showed T stage (TMN classification), N stage (TNM classification), and LLD were found to be significantly related to the rates of both cumulative survival and disease-free survival. That mean LLD was identified as a significant prognostic factor. But disease-free survival did not differ significantly between the patients who underwent LLD and those who did not undergo LLD in stage I, II, or III disease (p = 0.3681, p = 0.1815, and p = 0.0896, respectively). The local recurrence rate was similar in patients who received LLD (17.5 percent) and in those who did not receive LLD (23.1 percent; p = 0.498). But 7 patients with lateral lymph node metastasis (33.3 percent) remained disease free. And these patients had local lateral lymph node metastasis and benefited from LLD. CONCLUSIONS: LLD can substantially improve outcomes in selected patients at high risk for lateral lymph node metastasis. A randomized controlled clinical study is necessary to clarify the role of LLD in the treatment of rectal cancer.     

Laparoscopic lateral lymph node dissection in two fascial spaces for locally advanced lower rectal cancer

BACKGROUNDThe procedure for lateral lymph node (LLN) dissection (LLND) is complicated and can result in complications. We developed a technique for laparoscopic LLND based on two fascial spaces to simplify the procedure.AIMTo clarify the anatomical basis of laparoscopic LLND in two fascial spaces and to evaluate its efficacy and safety in treating locally advanced low rectal cancer (LALRC).METHODSCadaveric dissection was performed on 24 pelvises, and the fascial composition related to LLND was observed and described. Three dimensional-laparoscopic total mesorectal excision with LLND was performed in 20 patients with LALRC, and their clinical data were analyzed.RESULTSThe cadaver study showed that the fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side in a medial-lateral direction constituting the dissection plane for curative rectal cancer surgery, and the last three fasciae formed two spaces (Latzko''s pararectal space and paravesical space) which were the surgical area for LLND. Laparoscopic LLND in two fascial spaces was performed successfully in all 20 patients. The median operating time, blood loss and postoperative hospitalization were 178 (152-243) min, 55 (25-150) mL and 10 (7-20) d, respectively. The median number of harvested LLNs was 8.6 (6-12), and pathologically positive LLN metastasis was confirmed in 7 (35.0%) cases. Postoperative complications included lower limb pain in 1 case and lymph leakage in 1 case.CONCLUSIONOur preliminary surgical experience suggests that laparoscopic LLND based on fascial spaces is a feasible, effective and safe procedure for treating LALRC.     

Incidence and prognosis of lower rectal cancer with limited extramesorectal lymph node metastasis

Purpose

Patients with lower rectal cancer occasionally have limited extramesorectal lymph node metastasis. However, the incidence and prognosis of lower rectal cancer with limited extramesorectal lymph node metastasis remain unclear.

Methods

A total of 714 patients with clinical stage II or III lower rectal cancer who underwent extramesorectal lymph node dissection at the National Cancer Center Hospital between 1985 and 2011 were reviewed.

Results

Among the 714 patients with lower rectal cancer, 35 (4.9 %) had limited extramesorectal lymph node metastasis, of whom 28 (80.0 %) had one or two extramesorectal lymph node metastases. The 5-year overall survival rate was 74.5 %. The number of extramesorectal lymph node metastases was a significant prognostic factor. The 5-year overall survival rate of patients with three or more extramesorectal lymph node metastases was 28.6 %.

Conclusions

The incidence of limited extramesorectal lymph node metastasis in patients with lower rectal cancer was 4.9 %. Although the prognosis of patients with one or two extramesorectal lymph node metastases was favorable, that of patients with three or more such metastases was unfavorable.     

Laparoscopy-assisted lateral pelvic lymph node dissection for advanced rectal cancer

In Japan, there has been no indication of laparoscopic surgery for advanced lower rectal cancer because of the problem about the treatment of lateral pelvic lymph node metastasis. We report a new technique which allows lateral pelvic lymph node dissection like in open surgery for advanced rectal cancer. After laparoscopic total mesorectal excision for rectal cancer, a surgical incision of approximately 8 cm is placed in the supra-pubic area. Then, the latero-vesical area of the retroperitoneum, latero-vesical space is dissected bluntly with forceps. The external iliac artery and vein are taped and lymph node dissection is performed. As the external iliac vein is pulled internally, fatty tissue including lymph nodes in the obturator space is separated from the psoas major muscle. After completing of such a procedure, the obturator nerve is indentified in the fatty tissue with surrounding lymph nodes. As the external iliac vein is pulled laterally, fatty tissue including lymph nodes in the oburator space is dissected by fat aspiration procedure (FAP) using a suction tip. FAP is helpful to confirm the vascular system, by which the obturator space is skeletonized and anatomical structures are identified clearly.     

Preoperative lymph node staging in rectal cancer: a difficult challenge

The specimens of 59 rectal cancers that had been scanned by preoperative endorectal ultrasound (eus) were analysed by the pathologist in order to draw a map of the pararectal lymph nodes that should be detected by preoperative staging. 389 lymph nodes (LNs) were detected in the mesorectum, close to the tumour. Malignant LNs were larger than the non invaded: 17% of the LNs less than 6 mm in diameter were invaded whereas 23% of the LNs 6 mm or more in diameter were free of metastatic invasion. The non invaded LNs displayed three main patterns: follicle, sinusoidal and mixted types. Metastatic LNs were partially (n = 25) or totally (n = 76) invaded by tumoural cells. Diffuse involvement includes 4 different patterns: cellular proliferation, fibrosis, necrosis and cyst formation. Accuracy of EUS evaluated by a ``patient by patient' comparison was 61%, with a sensitivity of 84% and a specificity of 39%. However, a comparison ``lymph node by lymph node' showed a detection rate of 21% of the lymph nodes of 3 mm and more. It is concluded that a low percentage of LNs are detected by EUS in our experience. Metastatic and non metastatic LNs exhibit a great variety of morphological features and it seems difficult to reliably correlate metastatic invasion with a specific endosonic appearance. LN size remains the most reliable parameter.

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Résumé. Les pièces opératoires de 59 patients porteurs de cancer du rectum et qui avaient subi une échographie endo-anale pré-opératoire ont été analysées par le pathologue afin d'établir une cartographie des ganglions lymphatiques para-rectaux qui auraient pu être détectés lors du staging pré-opératoire. Trois-cent-quatre-vingt-neuf ganglions lymphatiques ont été identifiés dans le méso-rectum à proximité de la tumeur. Les ganglions lymphatiques métastatiques étaient plus volumineux que ceux non métastatiques: 17% des ganglions de moins de 6 mm de diamètre étaient infiltrés alors que 23% des ganglions de 6 mm et plus étaient libres de métastases. Les ganglions lymphatiques non métastatiques présentaient 3 types principaux: folliculaires, sinuso?daux et mixtes. Les ganglions métastatiques étaient partiellement (n = 25) ou totalement (n = 76) infiltrés de cellules tumorales. Les infiltrations diffuses présentaient 4 aspects principaux: prolifération cellulaire, fibrose, nécrose et formation kystique. L'exactitude de l'ultrasonographie comparée patient par patient était de 61% avec une sensibilité de 84% et une spécificité de 39%. Toutefois une comparaison de ganglion à ganglion montre un taux de détection de 21% des ganglions de 3 mm et plus. Il est conclu que dans notre expérience, un faible taux de ganglions sont repérés à l'ultrasonographie. Les ganglions métastatiques et non métastatiques présentent une grande variété de types morphologiques et il semble difficile de corréler de manière fiable l'infiltration métastatique avec un aspect ultrasonographique spécifique. La taille des ganglions reste le paramètre le plus fiable.

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Accepted: 20 June 1996     

Radiomics for differentiating tumor deposits from lymph node metastasis in rectal cancer

BACKGROUNDTumor deposits (TDs) are not equivalent to lymph node (LN) metastasis (LNM) but have become independent adverse prognostic factors in patients with rectal cancer (RC). Although preoperatively differentiating TDs and LNMs is helpful in designing individualized treatment strategies and achieving improved prognoses, it is a challenging task.AIMTo establish a computed tomography (CT)-based radiomics model for preoperatively differentiating TDs from LNM in patients with RC.METHODSThis study retrospectively enrolled 219 patients with RC [TDs⁺LNM^- (n = 89); LNM⁺ TDs^- (n = 115); TDs⁺LNM⁺ (n = 15)] from a single center between September 2016 and September 2021. Single-positive patients (i.e., TDs⁺LNM^- and LNM⁺TDs^-) were classified into the training (n = 163) and validation (n = 41) sets. We extracted numerous features from the enhanced CT (region 1: The main tumor; region 2: The largest peritumoral nodule). After deleting redundant features, three feature selection methods and three machine learning methods were used to select the best-performing classifier as the radiomics model (Rad-score). After validating Rad-score, its performance was further evaluated in the field of diagnosing double-positive patients (i.e., TDs⁺LNM⁺) by outlining all peritumoral nodules with diameter (short-axis) > 3 mm.RESULTSRad-score 1 (radiomics signature of the main tumor) had an area under the curve (AUC) of 0.768 on the training dataset and 0.700 on the validation dataset. Rad-score 2 (radiomics signature of the largest peritumoral nodule) had a higher AUC (training set: 0.940; validation set: 0.918) than Rad-score 1. Clinical factors, including age, gender, location of RC, tumor markers, and radiological features of the largest peritumoral nodule, were excluded by logistic regression. Thus, the combined model was comprised of Rad-scores of 1 and 2. Considering that the combined model had similar AUCs with Rad-score 2 (P = 0.134 in the training set and 0.594 in the validation set), Rad-score 2 was used as the final model. For the diagnosis of double-positive patients in the mixed group [TDs⁺LNM⁺ (n = 15); single-positive (n = 15)], Rad-score 2 demonstrated moderate performance (sensitivity, 73.3%; specificity, 66.6%; and accuracy, 70.0%).CONCLUSIONRadiomics analysis based on the largest peritumoral nodule can be helpful in preoperatively differentiating between TDs and LNM.     

Outcomes and prognostic factors of selective lateral pelvic lymph node dissection with preoperative chemoradiotherapy for locally advanced rectal cancer

Purpose

The clinical significance of preoperative chemoradiotherapy (CRT) and lateral lymph node dissection (LLND) for locally advanced rectal cancer remains unclear. We have employed total mesorectal excision and selective LLND following preoperative CRT for patients with locally advanced rectal cancer. The validity of our strategy was evaluated.

Methods

A total of 45 patients with locally advanced rectal cancer who underwent curative surgery after CRT from November 2005 to September 2016 were retrospectively analyzed. LLND was performed only for the patients with lateral lymph nodes suspected to have metastasis based on the pretreatment images.

Results

Rates of 5-year overall survival (OS) and 5-year relapse-free survival (RFS) were 85.7 and 61.8%, respectively. Univariate and multivariate analyses detected only histological response (grades 2 and 3 vs. grade 1) as a significant prognostic factor for OS and local recurrence. ypN and ypStage were significant factors for RFS by univariate analysis, while no significant factor was detected by multivariate analysis. There was no significant factor for distant recurrence. In good responders (grades 2 and 3), the local recurrence rate was 0% (P?=?0.006, vs. grade 1), while distant recurrence developed in 4 of 20 cases (20%, P?=?0.615, vs. grade 1). There was no local recurrence in LLND (?) group regardless the histological response.

Conclusions

Although selective LLND with preoperative CRT seems effective and valid for good responders, new treatment strategy is necessary for poor responders. Therefore, development of reliable biomarkers for histological response to CRT is an urgent need.

     

直肠癌侧方淋巴结清扫中国临床开展的现状

尽管目前东西方对于直肠癌侧方淋巴结清扫仍存争议,但中国学术界依据现有的循证医学证据制定了符合中国国情的侧方淋巴结清扫相关共识、指南和规范。相较于日本,国内侧方淋巴结清扫指征把握更加严格,仅当有明确影像学证据疑诊存在侧方淋巴结转移时,才会选择性进行清扫,常规清扫区域也仅限于髂内和闭孔周围。基于全面了解盆腔解剖结构的前提下,以筋膜为导向的两间隙清扫现已成为中国侧方淋巴结清扫的主流方案,该术式在明确清扫边界、保护神经功能、彻底清除侧方淋巴结等方面具有明显优势。未来随着更多的高质量侧方淋巴结清扫研究的进行,将会有更多的证据来规范直肠癌侧方淋巴结清扫的临床应用。     

Surgical treatment for isolated inguinal lymph node metastasis in lower rectal adenocarcinoma patients improves outcome

Purpose

No consensus has been formed on the optimal treatment strategy for the prognosis of patients with inguinal lymph node (ILN) metastasis from lower rectal adenocarcinoma. We, therefore, retrospectively analyzed outcomes of patients with ILN metastasis from lower rectal adenocarcinoma.

Methods

Of 323 patients with lower rectal adenocarcinoma treated at a single institution between November 1993 and March 2010, 10 had synchronous or metachronous ILN metastasis, as confirmed by curative resection (R0) of the primary lesion. Outcomes of these 10 patients were assessed.

Results

The 10 patients with ILN metastasis were divided into two groups: group A (two patients who did not undergo ILN resection surgery because of metastases at other sites) and group B (eight patients with no other metastases who underwent surgery). Both patients in group A, with median overall survival of 5.2 months, died due to the other metastases, whereas five out of eight patients in group B survived (P?=?0.001). Group B patients were further subclassified into synchronous (group B1) and metachronous (group B2) metastasis (n?=?4 each) groups. Two patients in group B1 died of other metastases, which was diagnosed later, whereas three patients in group B2 survived.

Conclusions

Some patients with isolated inguinal lymph node metastasis show a good prognosis after lymph node excision and, therefore, should be treated surgically. Patients with metachronous metastases have a better prognosis than patients with synchronous ILN metastases. Nevertheless, assessment of additional patients for prognosis and treatment strategy is warranted.