Role of Intraoperative Frozen Section Assessment of Proximal Bile Duct Margins and the Impact of Additional Re-Resection in Perihilar Cholangiocarcinomas.

Intraoperative frozen section (FS) analysis to assess the bile duct margin status is commonly used to assess the completeness of resection during surgery for perihilar cholangiocarcinoma (pCCA) resection. However, the impact of additional re-section on the long-term outcome after obtaining an initial positive margin remains unclear. Patients diagnosed as pCCA on preoperative imaging and subjected to curative intent surgery from May 2013 to June 2021 with a minimum follow-up of 2 years were included. Intraoperative FS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of invasive cancer. Out of the 62 patients with a preoperative diagnosis of pCCA on imaging, 35 patients were included for final analyses after excluding patients with inoperable disease (on staging laparoscopy or local exploration) and other/benign pathology on the final histopathology report. Out of the 35 patients, patients with postoperative 90-day mortality were excluded from the final survival analysis. FS analysis revealed an initial positive margin in 10 (28.5%) patients. Among 10 patients who underwent re-resection to achieve negative proximal margins, only 5 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes. Median disease-free survival (DFS) and overall survival (OS) were 16 and 19.6 months for patients with an initial positive margin, but 36 and 58.2 months for patients with an initial negative margin, respectively (p = 0.012). The median DFS and OS were significantly lower for those with secondary R0 as compared to primary R0 (16 vs. 36 months for DFS, p = 0.117 and 19.6 vs. 58.2 months for OS, p = 0.027, respectively). An intraoperative FS positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable pCCA. Additional resection has a questionable benefit on survival, when a secondary negative margin is achieved.

Impact of surgical proximal and distal margins on the recurrence of resectable colon cancer: a single-center observational cohort study.

PURPOSE: Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. METHODS: We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. RESULTS: Patients who had pT4 colon cancer with margins of more than 7 cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20-0.89). Multivariate analysis identified a margin of < 7 cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013-6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. CONCLUSION: A resection margin of at least 7 cm should be maintained for patients with pT4 colon cancer.

A systematic review of minimal length of lroximal margin in gastric adenocarcinoma resection.

For early distal gastric cancers, a proximal margin (PM) > 2-3 cm might probably be sufficient. For advanced tumors, many confounding factors have a prognostic impact on survival and recurrence and negative margin involvement may be more relevant than negative margin length. INTRODUCTION: In gastric cancer surgery, microscopic positive margin is a poor prognostic factor whereas complete resection with tumor-free margins remains a challenging issue. European guidelines recommended a macroscopic margin of 5 or even 8 cm for diffuse-type cancers to achieve R0 resection. However, it is unclear if the length of negative proximal margin (PM) could have a prognostic impact on survival. We aimed to perform a systematic review of the literature analyzing PM length and its prognostic impact in gastric adenocarcinoma. MATERIAL AND METHODS: Pubmed and Embase databases were searched for "gastric cancer" or "gastric adenocarcinoma," combined with "proximal margin," between January 1990 and June 2021. English-written studies that specified PM length were included. Survival data, in relation to PM, were extracted. RESULTS: Twelve retrospective studies, with a total number of 10,067 patients, met inclusion criteria and were analyzed. Mean length of proximal margin on the whole population varied from 2.6 to 5.29 cm. Three studies found minimal PM cut-off to improve overall survival in univariate analysis. Concerning recurrence-free survival analysis, only 2 series showed better results with PM > 2 or > 3 cm, using Kaplan-Meier method. Multivariate analysis demonstrated an independent impact of PM on overall survival in 2 studies. CONCLUSION: For early distal gastric cancers, a PM > 2-3 cm might probably be sufficient. For advanced or proximal tumors, many confounding factors have a prognostic impact on survival and recurrence and negative margin involvement may be more relevant than negative margin length.

Required esophageal resection length beyond the tumor boundary to ensure a negative proximal margin for gastric cancer with gross esophageal invasion or esophagogastric junction cancer.

BACKGROUND: To obtain a pathologically negative proximal margin (PM) for gastric cancer with gross esophageal invasion (EI) or esophagogastric junction (EGJ) cancer, we should transect the esophagus beyond the proximal boundary of gross EI with a safety margin because of a discrepancy between the gross and pathological boundaries of cancer. However, recommendations regarding the esophageal resection length for these cancers have not been established. METHODS: Patients who underwent proximal or total gastrectomy for gastric cancer with gross EI or EGJ cancer were enrolled. A parameter ΔPM, which corresponded to the length of a discrepancy between the gross and pathological proximal boundary of the tumor, was evaluated. The maximum ΔPM, which corresponded to the minimum length ensuring a pathologically negative PM, was first determined in all patients. Then subgroup analyses according to factors associated with ΔPM ≥ 10 mm were performed to identify alternative maximum ΔPMs. RESULTS: A total of 289 patients with gastric cancer with gross EI or EGJ cancer were eligible and analyzed in this study. The maximum ΔPM was 25 mm. Clinical tumor (cTumor) size and growth and pathological types were independently associated with ΔPM ≥ 10 mm. In subgroup analyses, the maximum ΔPM was 15 mm for cTumor size ≤ 40 mm and superficial growth type. Furthermore, the maximum ΔPM was 20 mm in the expansive growth type. CONCLUSIONS: Required esophageal resection lengths to ensure a pathologically negative PM for gastric cancer with gross EI or EGJ cancer are proposed.

Minimal length of proximal resection margin in adenocarcinoma of the esophagogastric junction: a systematic review of the literature.

The minimal length of proximal margin (PM) in esophagogastric junction cancer has not been established yet and its impact on patient survival remains unclear. Pubmed, Embase and Scopus databases were searched for "adenocarcinoma of the esophagogastric junction", "adenocarcinoma of the gastroesophageal junction" and "cardia cancer", each combined with "proximal margin". English written studies that specified PM length in AEG were included. Survival data in relation to PM were extracted. 13 studies, that were all retrospective case series, with a total number of 2648 patients met inclusion criteria and were analyzed. While 93% of 230 patients with Siewert type I had esophagectomy, 69% of 1270 patients with Siewert type II and 93% of 872 patients with Siewert type III had transhiatal extended gastrectomy. Minimal PM length was treated by five studies and ranged between 2 and 6 cm. While three studies defined minimal PM by the necessary length to obtain R0 resection, two studies found minimal PM length significantly associated with survival. Multivariate analyses revealed in two studies an independent impact of PM on survival, whereas one study did not found any significant relation between PM and survival. One study showed that PM length was significantly associated with survival in T2-4N0-2 tumors, but not in T1 or N3 tumors. In conclusion, available retrospective studies did not allow a conclusion for a minimal length of PM and showed no clear evidence for an impact of PM length on survival. Taking into consideration available data and the shrinkage phenomen, a PM > 2 cm might be necessary to obtain a sufficient PM.

Application of preoperative endoscopic ultrasonography localization in adenocarcinoma of the esophagogastric junction / 中华胸心血管外科杂志

Objective@#Preliminary study on the clinical effect of preoperative ultrasound endoscopy combined with staining labeling technique to locate the actual boundary of esophageal and gastric cancer@*Methods@#From September 1, 2015 to October 30, 2017, 18 patients with esophageal adenocarcinoma were enrolled in this study. The actual boundaries of esophageal and gastric-derived adenocarcinoma lesions were localized by endoscopic ultrasonography and staining. There were 10 males and 8 females. After completing the preoperative examination, 1-2 days before operation, endoscopic ultrasonography was used to locate the edge of the lesion. Two point injection of carbon nano suspension was used to mark the location of 1cm at the longest distance from the longitudinal axis of the tumor. According to the length of longitudinal axial staining, the thoracotomy was performed. Intraoperative proximal margin resection was used to send frozen pathology. According to the results of freezing, the operation was decided. After the operation, the specimens from the margin of the tumor were segmented into paraffin section, which was about 0.5cm in each segment, and the tumor cells were observed under the electron microscope at all levels of the paraffin sections.@*Results@#The average time of preoperative endoscopic ultrasonography staining was(10.16±1.38) min, and the diameter of nano carbon diffusion was(1.43±0.41)cm. All patients in the operation could clearly see the nano carbon staining area under the naked eye. In the field, the average time of locating lesions was(1.27±0.53)min. 5 patients underwent thoracoabdominal surgery and 13 underwent abdominal surgery. The average length of the cut margin of the tumor was(4.74±1.12)cm, and the frozen pathology of the incision margin was negative, and no additional operation was performed. The routine pathology confirmed that all the specimens were negative.@*Conclusion@#The staining and labeling technique for adenocarcinoma of the esophagogastric junction under endoscopic ultrasonography can detect the tumor edge and the scope of invasion accurately. It provides guidance and guarantee for the smooth implementation of AEG precision surgery. It is a safe, rapid and effective positioning technique.

Application of preoperative endoscopic ultrasonography localization in adenocarcinoma of the esophagogastric junction / 中华胸心血管外科杂志

Objective Preliminary study on the clinical effect of preoperative ultrasound endoscopy combined with stai-ning labeling technique to locate the actual boundary of esophageal and gastric cancer Methods From September 1, 2015 to October 30, 2017, 18 patients with esophageal adenocarcinoma were enrolled in this study. The actual boundaries of esophage-al and gastric-derived adenocarcinoma lesions were localized by endoscopic ultrasonography and staining. There were 10 males and 8 females. After completing the preoperative examination, 1-2 days before operation, endoscopic ultrasonography was used to locate the edge of the lesion. Two point injection of carbon nano suspension was used to mark the location of 1cm at the lon-gest distance from the longitudinal axis of the tumor. According to the length of longitudinal axial staining, the thoracotomy was performed. Intraoperative proximal margin resection was used to send frozen pathology. According to the results of freezing, the operation was decided. After the operation, the specimens from the margin of the tumor were segmented into paraffin section, which was about 0. 5cm in each segment, and the tumor cells were observed under the electron microscope at all levels of the paraffin sections. Results The average time of preoperative endoscopic ultrasonography staining was(10. 16 ± 1. 38) min, and the diameter of nano carbon diffusion was(1.43 ±0.41)cm. All patients in the operation could clearly see the nano carbon staining area under the naked eye. In the field, the average time of locating lesions was(1.27 ±0.53)min. 5 patients under-went thoracoabdominal surgery and 13 underwent abdominal surgery. The average length of the cut margin of the tumor was(4. 74 ±1.12)cm, and the frozen pathology of the incision margin was negative, and no additional operation was performed. The routine pathology confirmed that all the specimens were negative. Conclusion The staining and labeling technique for adeno-carcinoma of the esophagogastric junction under endoscopic ultrasonography can detect the tumor edge and the scope of invasion accurately. It provides guidance and guarantee for the smooth implementation of AEG precision surgery. It is a safe, rapid and effective positioning technique.

Correlating pre-operative MRI measurements of metatarsal Osteomyelitis with surgical clean margins reveals the need for a one centimeter resection margin.

BACKGROUND: Due to the high incidence of forefoot ulcerations with associated osteomyelitis, there has been an increased demand for partial ray amputations. In order to ensure complete removal of infected metatarsal bone, a clean margin amount is chosen based on the surgeon's intraoperative visual subjective evaluation. The margin is resected and sent to pathology. Currently the literature shows positive proximal margin rates of 35-40%. The purpose of this study was to reduce the rate of positive proximal margins by effectively resecting all infected bone using pre-operative MRI measurements with an added resection margin. METHODS: Twenty-four osteomyelitis positive metatarsals were included in this exploratory study. The distance of proximal osteomyelitic extension within the metatarsal was measured on MRI in centimeters. Intra-operatively, the partial ray amputation cut was determined by adding an extra 0.5 cm resection margin to the MRI measurement. At the study's mid-point, bone histopathology revealed an increase in positive proximal margin rates-so the resection margin was increased to 1 cm. Descriptive outcomes included the mean distance of osteomyelitis propagation, proximal margin rates, as well as diagnostic statistics. RESULTS: After removing the specimens with false positive MRI results, the study sample included 21 metatarsals positive for osteomyelitis. A 0.5 cm resection margin proximal to the osteomyelitis resulted in a 50% positive proximal margin rate. After increasing the resection margin to 1 cm, there was found to be an improved positive proximal margin rate of 9%. Based on MRI findings, the mean distance + standard deviation of osteomyelitis propagation along the metatarsal proximally was 1.81 cm + 0.74 cm. The metatarsal specimen was processed by pathology into multiple pieces and compared to MRI, resulting in MRI sensitivity of 67%, specificity of 74%, positive predictive value of 79%, and negative predictive value of 60%. CONCLUSIONS: By performing a 1 cm resection margin proximal to the metatarsal osteomyelitis the proximal margin rate was reduced to clinically meaningful levels. These preliminary findings support using a 1 cm resection margin when performing any form of metatarsal amputation, to reduce the risk of residual osteomyelitis post-operatively. TRIAL REGISTRATION: St. Luke's Hospital, IRB National Protocol ID SLHN2015-112. Date:1-13-16.

Individualized proximal margin correlates with outcomes in gastric cancers with radical gastrectomy.

The length of proximal margin for gastrectomy remains controversial. The proximal margin and its relationships with clinicopathological variables and overall survival of 922 gastric cancers were retrospectively analyzed. Proximal margin was divided into four groups (0-2.0, 2.1-4.0, 4.1-6.0, and >6.0 cm). It indicated that the overall survival was improved with the increase of proximal margin. The proximal margin of 2.1-4.0 cm was associated with a better overall survival for gastric cancers with solitary-type (T1 and T2 stages, N0 stage, tumor-node-metastasis stages I and II, tumor size <5 cm, histological G1 and G2, and Bormann type I and II). Futhermore, proximal margin of 4.1-6.0 cm was associated with a better overall survival for gastric cancers with infiltrative-type (T3 and T4 stages, N1 stage, tumor-node-metastasis stage III, tumor size ⩾5 cm, histological G3 and G4, and Bormann type III and IV). Univariate analysis revealed that T stage, N stage, tumor-node-metastasis stage, histological grade, Bormann type, carcinoembryonic antigen, carbohydrate antigen 199, extent of gastrectomy, tumor location, and proximal margin were significantly associated with overall survival. Multivariate analysis revealed that tumor-node-metastasis stage, histological grade, Bormann type, carcinoembryonic antigen, carbohydrate antigen 199, extent of gastrectomy, and proximal margin were independent prognostic factors for gastric cancers with radical gastrectomy. In conclusion, the proximal margin was an independent prognostic factor for gastric cancer and should be decided individually. Proximal margin of 2.1-4.0 cm and 4.1-6.0 cm were needed for patients with solitary-type and infiltrative-type, respectively.

The length of proximal margin does not influence the prognosis of Siewert type II/III adenocarcinoma of esophagogastric junction after transhiatal curative gastrectomy.

BACKGROUND: The optimal length of proximal margin for Siewert type II/III adenocarcinoma of the esophagogastric junction (AEJ) is still need to be clarified. The aim of the present study was to investigate the appropriate length of proximal margin for Siewert type II/III AEJ through transhiatal approach. METHODS: From September 2009 to December 2014, a total of 693 consecutive patients with Siewert type II/III AEJ were retrospectively analyzed. All patients received transhiatal R0 resection. The proximal margin length was measured immediately after resection. The prognostic value of proximal margin length on Siewert type II/III AEJ with transhiatal approach was analyzed. RESULTS: There were 404 cases of Siewert type II AEJ (58.3 %) and 289 cases of Siewert type III AEJ (41.7 %). Total gastrectomy was performed in 526 patients (75.9 %), and proximal gastrectomy was performed in 167 patients (24.1 %). The median length of the gross proximal margin was 2.4 (range 0.1-5.0) cm. Lymph node metastasis was the only independent prognostic predictor for Siewert type II AEJ. Tumor size and lymph node metastasis were independent prognostic predictors for Siewert type III AEJ. CONCLUSIONS: For Siewert type II/III AEJ with esophageal invasion of 3 cm or less, proximal margin length does not influence the prognosis of patients after transhiatal curative gastrectomy.

The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative.

BACKGROUND: A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established. METHODS: Patients who underwent curative-intent resection for proximal GAC from 2000 to 2012 at 7 centers in the US Gastric Cancer Collaborative were included. PM length was sequentially dichotomized and analyzed at 0.5 cm increments (0.5-6.5 cm). Outcomes after negative margin (R0) and positive microscopic margin (R1) resections were compared. Primary endpoints were local recurrence (LR) and overall survival (OS). RESULTS: All patients (n = 162) had R0 distal margins. 151 (93.2%) had an R0-PM with mean length of 2.6 cm (median:1.7 cm; range:0.1-15 cm). A greater PM distance was not associated with LR or OS. An R1-PM was associated with higher N-stage (N3:73% vs. 26%; P = 0.007) and increased LR (HR6.1; P = 0.009) but not associated with decreased OS. On multivariate analysis, an R1-PM was also not independently associated with LR. CONCLUSIONS: For resection of proximal gastric adenocarcinoma, proximal margin length is not associated with local recurrence or overall survival. An R1 margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing resection of proximal gastric adenocarcinoma, efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned.

The distance of proximal resection margin dose not significantly influence on the prognosis of gastric cancer patients after curative resection.

PURPOSE: It is well known that the curative resection with an adequate proximal margin length is the most effective treatment in gastric cancer. However, despite surgeon's effort to achieve a sufficient proximal margin length, it is often difficult to obtain a recommended proximal margin length in some cases. Therefore, this study was planned to investigate the impact of the length of proximal margin on prognosis of overall survival. METHODS: Between June 1992 and December 2010, 1,888 gastric cancer patients who underwent gastrectomy with curative intent were reviewed. According to tumor's location (total vs. subtotal gastrectomy), pathologic T staging, and differentiation, univariate and multivariate analyses were performed to evaluate the impact of the discrepancies of proximal margin length on overall survival. Also, the impact of the discrepancies of proximal margin length on local recurrence was assessed. RESULTS: The 5-year survival rate of positive proximal margin group was 5.9%. In negative proximal margin groups, multivariate analysis showed that the discrepancies of proximal margin length have no impact on overall survival. Kaplan-Meier analyses showed that there is no association between discrepancy of proximal margin length and local recurrence. CONCLUSION: It takes effort to secure a negative proximal margin in the surgical treatment of gastric cancer because of the poor prognosis of positive proximal margin. In negative proximal margin patients, there's no need to achieve an additional proximal margin length for long-term survival benefit because there was no impact of proximal margin length on overall survival and local recurrence.

The distance of proximal resection margin dose not significantly influence on the prognosis of gastric cancer patients after curative resection

PURPOSE: It is well known that the curative resection with an adequate proximal margin length is the most effective treatment in gastric cancer. However, despite surgeon's effort to achieve a sufficient proximal margin length, it is often difficult to obtain a recommended proximal margin length in some cases. Therefore, this study was planned to investigate the impact of the length of proximal margin on prognosis of overall survival. METHODS: Between June 1992 and December 2010, 1,888 gastric cancer patients who underwent gastrectomy with curative intent were reviewed. According to tumor's location (total vs. subtotal gastrectomy), pathologic T staging, and differentiation, univariate and multivariate analyses were performed to evaluate the impact of the discrepancies of proximal margin length on overall survival. Also, the impact of the discrepancies of proximal margin length on local recurrence was assessed. RESULTS: The 5-year survival rate of positive proximal margin group was 5.9%. In negative proximal margin groups, multivariate analysis showed that the discrepancies of proximal margin length have no impact on overall survival. Kaplan-Meier analyses showed that there is no association between discrepancy of proximal margin length and local recurrence. CONCLUSION: It takes effort to secure a negative proximal margin in the surgical treatment of gastric cancer because of the poor prognosis of positive proximal margin. In negative proximal margin patients, there's no need to achieve an additional proximal margin length for long-term survival benefit because there was no impact of proximal margin length on overall survival and local recurrence.