Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma

Aims

Despite curative surgery for pancreatic ductal adenocarcinoma (PDAC), most patients develop cancer recurrence and die from metastatic disease. Understanding of the patterns of failure after surgery can lead to new insights for novel therapeutic modalities. The aim of the present study is to describe the patterns of recurrence after curative resection of PDAC.

Methods

A retrospective analysis was performed of 145 consecutive resections for PDAC between 1998 and 2005 (M/F 75/70; median (range) age 67 years (32–85 y)). The location of the first and consecutive recurrences, and the time interval to cancer recurrence after surgical resection was studied. The magnitude of tumour-free margin was less than a millimetre in 48 patients, whereas a positive surgical margin was observed in 27 patients. The median duration of follow-up was 18.5 (range 0.3–116.8) months.

Results

Cancer recurrence was observed in 110 patients. The first location of recurrence was locoregional in 19, extra-pancreatic in 66, and combined locoregional and extra-pancreatic in 25 patients. Extra-pancreatic recurrence developed in the liver in 57, peritoneal in 35, pulmonary in 15, and retroperitoneal in 5 patients. The median (95% CI) overall (OS) and disease-free (DFS) survival was 18.7 (15.7–23.5) and 9.8 (7.5–12.4) months, respectively. The type of cancer recurrence did not significantly influence OS, while the resection margin status had a prognostic effect.

Conclusion

The vast majority of patients who undergo potentially curative surgery for PDAC develop cancer recurrence located in the abdominal cavity. Surgical resection margins with tumour involvement and tumour-free margins of less then 1 mm are negative prognostic factors. Further research on better local surgical control, peri-operative locoregional treatment, and more effective adjuvant systemic therapy is necessary to improve long-term survival of patients with curable PDAC.     

‘Close Shave’ in liver resection for colorectal liver metastases

Introduction

The optimal size of clear liver resection margin width in patients with colorectal liver metastases (CRLM) remains controversial. The aim of this study was to investigate the effects of margin width on long-term survival after liver resection for CRLM with a policy of standard neo-adjuvant chemotherapy.

Methods

Consecutive patients (n = 238) who underwent liver resection for CRLM were included over a ten-year period. All patients with synchronous or early (<2 years) metachronous tumours were treated with neo-adjuvant chemotherapy. Data were recorded prospectively.

Results

Overall survival of the cohort at 1, 3 and 5 years were 90.3%, 68.1% and 56.1% respectively. The incidence of cancer involved resection margins (CIRM) was 5.8%. Patients with macroscopically involved resection margins had a poorer overall survival than those with microscopically involved margins (p = 0.04). Involved resection margins had a poorer overall survival (p = 0.002) than patients with clear margins. Width of clear resection margin did not affect long-term survival.

Conclusion

CIRM independently predicts poor outcome in patients with CRLM. Clear margin width does not affect survival. A standard policy of neo-adjuvant chemotherapy may be associated with a low incidence of CIRM and improved long-term outcome of sub-centimetre margin widths, resembling those with >1 cm resection margins.     

Prognostic improvement of reexcision for positive resection margins in patients with advanced gastric cancer

Aim

The aim of this study was to investigate the effect of reexcision for advanced gastric cancer (GC) with positive resection margins on prognosis and to identify the selection criteria for the reexcision of patients with positive margins.

Patients and methods

This was a retrospective study of 122 patients with positive margins who underwent potentially curative resection for locally advanced GC. The clinicopathological factors and survival among 50 patients who were reexcised to a negative resection margin (NR group) and 72 patients who were left with a positive resection margin (PR group) were compared using univariate and multivariate analyses.

Results

Median survival in the PR group was 18 months compared with 23 months in the NR group (p = 0.019). In the ≤pN2-category subset, the PR group had a significantly worse prognosis compared with the NR group (median survival of 25 months vs. 44 months; p = 0.021). This difference was not observed in the pN3-category subset. In the univariate analysis, variables including pTNM stage, pN-category, and positive resection margin had adverse effects on OS among the entire population of 122 patients. A positive margin was confirmed as an independent prognostic factor for OS in the multivariate analysis.

Conclusions

The reexcision of a positive margin improves the prognosis of patients with advanced GC, especially in those paitents with ≤pN2-category disease and in patients undergoing D2 lymphadenectomy. Obtaining routine frozen sections of samples from the resection margin should be mandatory in the treatment of all GC patients undergoing potentially curative surgery.     

Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma – A single-center experience

Aims

The aim of this study is to evaluate factors associated with the outcome after surgical resection and to compare the efficacy of surgery to transarterial chemoembolisation (TACE) in patients with advanced intrahepatic cholangiocarcinoma (IHC).

Materials and methods

273 patients with IHC treated in our department between 1997 and 2012 were included in our study. Patients were divided according to therapy into surgical (n = 130), TACE (n = 32), and systemic chemotherapy/best supportive care (n = 111) groups. Clinicopathological characteristics and survival were reviewed retrospectively.

Results

The 1-, 3-, and 5-year survival rates in patients after surgical resection were 60%, 40%, and 23%, respectively. Recurrence occurred in 63 percent of patients after R0 resection. Median time of recurrence-free survival was 14 months. Univariate analysis revealed nine significant risk factors for overall survival in the resection group: major surgery, extrahepatic resection, vascular and bile duct resection, lymph node invasion, poor tumour differentiation, positive surgical margin, multiple lesions, tumour diameter, and UICC-Stage. Multivariate analysis showed that lymph node metastasis (P < 0.001), poor tumour differentiation (P = 0.002), and positive resection margins (P = 0.001) were independent prognostic factors for survival. Median survival as well as overall survival rates of TACE patients were comparable to those of lymph node positive patients and patients with tumour positive surgical margins.

Conclusions

R0 resection in patients with negative lymph node status remains the best chance for long-term survival in patients with IHC. There is no significant survival benefit of surgery in lymph node positive patients or patients with positive resection margin over TACE.     

Systematic cavity shaving: Modifications of breast cancer management and long-term local recurrence,a multicentre study

Background

The status of the surgical margins of lumpectomy is one of the most important determinants of local recurrence in breast cancer. Systematically practicing cavity margin resection is debated but may avoid surgical re-excision and allow the diagnosis of multifocality.

Methods

This multicentric retrospective study included 294 patients who underwent conservative management of breast cancer with 2–4 systematic cavity shavings. Clinico-biological characteristics of the patients were collected in order to establish whether surgical management was modified by systematic cavity shaving. Local recurrence rate with a long-term follow up of minimum 4 years was evaluated.

Results

Cavity shaving avoided the need for re-excision in 25% of cases and helped in the diagnosis of multifocality in 8% of cases. Resection volume was not associated with usefulness of the cavity shaving. No predictive factor of positive cavity shaving was found. The rate of local recurrence was 3.7% and appeared in a median time of 3 years and 8 month. Only one quarter of the patients with local recurrence had initially positive lumpectomy margins but negative cavity shaving.

Discussion

Systematic cavity shaving can change surgical management of conservative treatment. No specific target population for useful cavity shaving was found, such that we recommend utilising it systematically.     

Dermatofibrosarcoma protuberans: Recurrence is related to the adequacy of surgical margins

Introduction

The aim of the study was to investigate the results of surgical treatment in primary and recurrent dermatofibrosarcoma protuberans (DFSP), with respect to local tumor control.

Patients and methods

Thirty-eight patients were treated between 1971 and 2005 at the University Medical Center Groningen (UMCG). Thirty patients presented with primary disease (79%) and 8 patients with locally recurrent disease (21%). The treatment consisted of surgical resection and in case of marginal or positive resection margins (R1 resection) adjuvant radiotherapy.

Results

Adequate surgical margins as a single modality was associated with 100% local control in all primary DFSPs. Two patients whose resection specimens had microscopically positive resection margins had withdrawn from adjuvant radiotherapy and developed local recurrence (LF rate 7%). Two of the 8 patients referred with a local recurrence developed a second recurrence (LF rate 25%); one of these patients developed distant disease and ultimately died of systemic disease. None of the five patients with DFSP-FS developed LF after treatment at the UMCG.After a median follow-up of 89 (12–271) months, the 10-year disease-free survival was 85% and the 10-year disease specific survival was 100%.

Conclusion

After wide surgical resection of a DFSP or DFSP-FS, or an R1 resection combined with adjuvant radiotherapy the risk of local recurrence is extremely low.     

Appraisal of a total meso-pancreatoduodenum excision with pancreaticoduodenectomy for pancreatic head carcinoma

Background

The most significant prognostic factors for pancreatic head carcinoma (PHC) with pancreaticoduodenectomy (PD) are the resection margin and lymph node status. The curative surgical margin (R0) and complete clearance of regional lymph nodes contribute to the improvement of survival. To reduce microscopic residual tumor resection (R1) and achieve a complete lymphadenectomy around the superior mesenteric artery (SMA) when performing a PD for PHC, we propose a new concept of a total excision of the “meso-pancreatoduodenum.” which consists of a cluster of the soft connective tissue along the inferior pancreaticoduodenal artery and the first jejunal artery.

Methods

A total of 39 consecutive patients underwent a PD for PHC between May 2006 and August 2011 at Shimane University Hospital. Twenty-five patients received a standard PD (sPD), while 14 cases underwent a total meso-pancreatoduodenum excision (tMPDe) with PD.

Results

The tMPDe procedure was performed safely without any intraoperative complications. The total number of lymph nodes dissected was 18 (median, range: 5–40) in the sPD and 26 (median, range: 13–50) in the tMPDe (p = 0.027). R0 resection was accomplished in 60% and 93% of patients with the sPD and tMPDe, respectively, resulting in a significant decrease in the R1 rate in the tMPDe (7%) compared to that in the sPD (40%) (p = 0.019). No loco-regional recurrence was found around the SMA in the tMPDe patients.

Conclusion

Our surgical technique, tMPDe, is safe and more radical when performing a PD and should be adopted when performing pancreatic surgery as a pathological cure for pancreatic head carcinoma.     

Radiofrequency assisted liver resection: analysis of 604 consecutive cases

Background

Intraoperative blood loss is an important factor contributing to morbidity and mortality in liver surgery. To address this we developed a bipolar radiofrequency (RF) device, the Habib 4X, used specifically for hepatic parenchymal transection. The aim of this study was to prospectively assess the peri-operative data using this technique.

Methods

Between 2001 and 2010, 604 consecutive patients underwent liver resections with the RF assisted technique. Clinico-pathological and outcome data were collected and analysed.

Results

There were 206 major and 398 minor hepatectomies. Median intraoperative blood loss was 155 (range 0–4300) ml, with a 12.6% rate of transfusion. There were 142 patients (23.5%) with postoperative complications; none had bleeding from the resection margin. Only one patient developed liver failure and the mortality rate was 1.8%.

Conclusions

RF assisted liver resection allows major and minor hepatectomies to be performed with minimal blood loss, low blood transfusion requirements, and reduced mortality and morbidity rates.     

A new measure to assess the difficulty of liver resection

Background

There is no valid measure to assess surgical difficulty and feasibility of a planned liver resection. It is the objective of this study to evaluate a mathematical measure from a 3D graphical analysis.

Methods

Eleven different 3D models of hepatic tumours were evaluated by experts for resectability and analysed with Amira^® graphic software taking into consideration the portal and hepatic venous vascular relationships. Virtual resection volumes with increasing resection margins from 1 to 30 mm were determined separately for portal veins, hepatic veins, their intersections and volume unions. The integral of the increasing resection volumes was defined as risk coefficient. The risk coefficients from this volumetric analysis were compared with the expert opinion.

Results

The risk coefficient based on the integral of portal venous and hepatic venous volume unions reproduced the expert opinion highly significantly (correlation coefficient 0.9, p < 0.05) and more accurately than volumetric analysis of the planned resection margin.

Conclusion

With automated volumetric analysis, anatomically problematic situations in liver surgery can be reproduced and scaled. The risk coefficient obtained is a suitable objective measure for defining risk areas in liver surgery.     

Involved anterior margins after breast conserving surgery: Is re-excision required?

Background

Complete tumour excision in breast conserving surgery (BCS) is critical for successful outcome; involved circumferential resection margins are associated with increased disease recurrence. However, the importance of an involved anterior margin (IAM) is less clear. The purpose of this study was to review an aggressive approach to IAM and hence assess whether anterior margin re-excision (RE) yields clinical benefit.

Methods

A review of prospectively collected clinical and pathology data was performed for all patients who underwent BCS between 2006 and 2010 through a single cancer centre. An involved margin was defined as <1 mm clearance of invasive or in-situ breast cancer.

Results

1667 patients underwent BCS for invasive and/or in-situ disease, of whom 114 underwent RE. A total of 170 involved margins were identified: most commonly the anterior (52 margins) followed by the posterior (39 margins) and inferior (31 margins) margin. Patients with IAM were more likely to have grade 3 invasive disease (p = 0.0323) but less likely to have residual disease found at re-excision (2/49 vs. 32/101 margins, p = 0.0033); there were no differences when in-situ characteristics were compared.

Conclusions

RE of IAM after BCS rarely yields further disease; multi-disciplinary teams should consider whether further therapy for an IAM is required on a patient by patient basis.     

A review of the surgical management of sacral chordoma

Background

Sacral chordomas are rare low-to-intermediate grade malignant tumours, which arise from remnants of the embryonic notochord. This review explores prognostic factors in the management of sacral chordomas and provides guidance on the optimal treatment regimens based on the current literature.

Patients and methods

Electronic searches were performed using MEDLINE, Embase and the Cochrane library to identify studies on prognostic factors in the management of sacral chordomas published between January 1970 and December 2013. The literature search and review process identified 100 articles that were included in the review article. This included both surgical and non-surgical studies on the management of sacral chordomas.

Results

Sacrectomy with wide resection margins forms the mainstay of treatment but is associated with high risk of disease recurrence and reduced long-term survival. Adequate resection margins may require sacrifice of adjacent nerve roots, musculature and ligaments leading to functional compromise and mechanical instability. Large tumour size (greater than 5–10 cm in diameter), dedifferentiation and greater cephalad tumour extension are associated with increased risk of disease recurrence and reduced survival. Chordomas are poorly responsive to conventional radiotherapy and chemotherapy.

Conclusion

Operative resection with wide resection margins offers the best long-term prognosis. Inadequate resection margins, large tumour size, dedifferentiation, and greater cephalad chordoma extension are associated with poor oncological outcomes. Routine long-term follow-up is essential to enable early detection and treatment of recurrent disease.     

Impact of hepatectomy margin on survival following resection of colorectal metastasis: The role of adjuvant therapy and its effects

Introduction

The optimal width of microscopic margin and the use of adjuvant therapy after a positive margin for hepatic resection for colorectal liver metastasis (CRCLM) has not been conclusively determined. The aim of the current study is to evaluate the influence of width of surgical margin and adjunctive therapy upon disease free and overall survival.

Methods

All patients undergoing hepatectomy for CRCLM from 1997 to 2012 were identified from a prospectively maintained, IRB approved database. Patients were divided into four subgroups based on the parenchymal margin: positive, <0.1 cm, 0.1 cm–1 cm, and >1 cm.

Results

A total of 373 patients were included for analysis with a median follow up of 26 months (range 9–103 months) and a median overall survival of 53 months. The resection margin was positive (26 patients median OS 24 months), <0.1 cm (48 patients median OS 36 mon), 0.1 cm–1 cm (82 patients median OS 44 months), and >1 cm (217 patients median OS 64 months). The most common adjunctive therapy was chemotherapy, hepatic arterial therapy, or local. Patients with positive margins also had the shortest disease free survival (DFS), 16 months. The DFS was similar amongst the other margin groups (<0.1 cm: 21 months, 0.1–1 cm: 22 months, >1 cm 25 months). Hepatectomy margin independently influenced survival (p = 0.017) and disease free survival (p = 0.034). Patients with negative margins has similar overall recurrence rates (p = 0.36) and survival rates (p = 0.89).

Conclusions

A positive surgical margin indicates a worse overall biology of disease for patients undergoing hepatectomy for CRCLM, and appropriate multi-disciplinary therapy should be considered in this high risk patient population. Marginal width if a complete resection has been achieved does not adversely effect overall surgical in patients with CRCLM.     

The use of CT derived solid modelling of the pelvis in planning cancer resections

Clinical problem

Resection of malignant tumors of the pelvis is demanding. To avoid disabling hemipelvectomies, years ago internal hemipelvectomy combined with partial pelvic replacements had become a surgical procedure. To achieve adequate reconstructions custom-made replacements were recommended. In early stages of the surgical procedure using megaprostheses, individual pelvic models were manufactured.

Aim of the study

Since little is known about the accuracy of such models we analysed the charts of 24 patients (25 models) for whom an individual model of the osseous pelvis had been manufactured.

Results

Two patients refused surgery. In 23 patients partial resection of the bony pelvis was performed followed by a partial pelvic replacement (13×), hip transposition procedure (5×), ilio-sacral resection (4×), or revision surgery.In all patients who received a partial pelvic replacement, the fit of the replacement was optimal. No major unplanned resection was necessary. The same was observed in patients who received a hip transposition procedure or an ilio-sacral resection.Oncologically, in most of the patients we achieved wide resection margins (14×). In 5 patients the margins were marginal (4×) or intralesional (1×). In two cases the aim was a palliative resection because of a metastatic disease (1×) or benign entity (1×).

Conclusion

Pelvic models are helpful tools to planning the manufacture of partial pelvic replacements and ensuring optimal osseous resection of the involved bone. Further attempts have to be made to evaluate the aim of navigational techniques regarding the accuracy of the osseous and soft-tissue resection.     

T-category reflects the histopathologic characteristics of gallbladder cancer

Aims

Gallbladder (GB) cancer is a relatively uncommon gastrointestinal malignancy and is known to often result in unfavorable outcomes. Recent advances in aggressive surgical resection have improved the overall survival rate of patients with GB cancer. We aimed to evaluate the outcomes and prognostic factors of GB cancer following a surgical resection with curative intent.

Methods

Between March 2001 and March 2009, 89 patients with GB cancer underwent surgical resection with curative intent at the National Cancer Center of Korea. We then conducted a retrospective analysis of clinicopathologic data.

Results

Nineteen patients underwent simple cholecystectomy and 70 patients underwent extended cholecystectomy. Tumor-free resection margins were obtained in 84 cases. The 1-, 3- and 5-year disease-specific survival rates in the 89 patients were 85.8%, 68.0% and 64.1%, respectively. By multivariate analysis, only the T-category was significant (p < 0.001). The T-category showed a close correlation with all of the other histopathologic factors which were significant in univariate analysis.

Conclusion

The T-category of GB cancer represents not only the depth of the primary tumor but also the aggressiveness of its histopathologic nature.     

Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma

Background

The most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT.

Methods

From January 1996 to December 2006, 64 patients with LAPA (borderline, n = 49; unresectable, n = 15) received 5-fluorouracil-cisplatin-based CRT. Of the 64 patients, 47 had progressive disease at restaging. Laparotomy was performed for 17 patients, and PD was performed in 9 patients (resected group). Fifty-five patients had CRT followed by gemcitabine-based chemotherapy (unresected group).

Results

The median survival and overall 5 years survival duration of all 64 patients were 14 months and 12%, respectively. The mean delay between diagnosis and surgical resection was 5.5 months. Mortality and morbidity from PD were 0% and 33%, respectively. The median survival of the resected group vs. the unresected group was 24 months vs. 13 months. Three specimens presented a major pathological response at histological examination. No involved margins were found and positive lymph nodes were found in one patient. Resected patients developed distant metastases.

Conclusions

PD after CRT was safe and resected patients had interesting survival rates. However, resected patients developed metastatic disease and new neoadjuvant regimens are needed to improve the survival of these patients.     

Radioguided Intraoperative Margins Evaluation (RIME): Preliminary results of a new technique to aid breast cancer resection

Aims

Women undergoing breast-conserving surgery for cancer can present residual disease. We have developed a technique called Radioguided Intraoperative Margins Evaluation (RIME) that uses a radiopharmaceutical to distinguish normal and cancer tissues. The aim of this study was to assess whether RIME is a feasible technique, and if it could help in breast cancer resection with free margins, minimizing residual disease.

Methods

Twenty-three breast cancer patients programmed for mastectomy were selected. Before surgery, the patients were submitted to scintimammography with ^99mTc-sestamibi to estimate the optimal time to begin radioguided surgery. Twenty patients were submitted to magnetic resonance imaging (MRI), to evaluate skin, deep fascia and to detect other tumor foci. At the beginning of the surgery, the same dose of ^99mTc-sestamibi was intravenously injected into patients. Tumor resection was performed under guidance of a gamma-probe, characterizing the RIME technique. Finally, modified radical mastectomy was performed. Tumor and residual breast were histopathologically examined.

Results

The RIME technique was successfully performed in all patients. The principal tumor was removed by this technique and provided 82.6% of histologically free margins (mean margins, 4.8 mm). Additionally, 47.8% of patients were without residual disease. The mean size of residual carcinoma was 3.67 mm and generally located near the tumor bed (<1.5 cm). There was no significant association between presence of residual disease and tumor size or margin status.

Conclusion

RIME is a feasible technique that could help tumor resection with free margins; however, it seems to be limited for small carcinoma foci.     

Prognostic factors for and prognostic value of mesenteric lymph node involvement in advanced-stage ovarian cancer

Aim of this study

To determine the prognosis of and prognostic factors for mesenteric node involvement in patients undergoing a bowel resection at the time of debulking surgery for primary treatment of advanced-stage ovarian cancer (ASOC).

Methods

A retrospective review of patients treated between 2005 and 2008 for ASOC and undergoing initial and interval debulking surgery with bowel resection (whatever the bowel segment). The characteristics and prognostic impact of mesenteric node involvement were studied.

Results

During the study period, 52 patients underwent debulking surgery for ASOC with bowel resection. Eighteen and 34 patients underwent initial or interval debulking surgery respectively. The most frequent site of the bowel resection was the rectosigmoid colon (38 patients; 73%) and 12 patients had resection of at least 2 intestinal segments. All patients had a complete macroscopic resection of peritoneal disease. Nineteen patients (37%) had mesenteric node involvement with a median of 4 involved nodes (range, 1–12). The degree of involvement of the intestinal wall and retroperitoneal node involvement (pelvic or para-aortic) had no impact on the risk of mesenteric node involvement. Overall survival and the location of recurrent disease were similar in patients with or without spread to mesenteric nodes.

Conclusions

This study suggests that mesenteric node involvement is frequent in patients undergoing bowel resection in ASOC. Such spread does not appear to have an impact on patient survival. Modifying peroperative (particularly the extent of the mesocolon resection) or postoperative management is therefore unnecessary.     

The differential response to chemotherapy of ovarian metastases from colorectal carcinoma

Patients and methods

All patients with metastatic (ovarian and extraovarian) CRC who underwent resection of ovarian metastases in our institution from April 1988 to August 2006 were analyzed and the response to preoperative chemotherapy was evaluated according to the RECIST criteria, and analyzed with respect to the sites of metastases (ovarian and extraovarian).

Results

The studied population consisted of 23 women. At presentation, 20 patients had symptoms. Preoperative chemotherapy resulted in tumor control of measurable extraovarian metastases in 65% of cases. In contrast, no objective tumor response of ovarian metastases was observed, disease stabilization was obtained in only 3 patients (13%), and progression or occurrence of new ovarian metastases were observed in 20 patients (87%) (p = 0.0005).With a median follow-up of 54 months [15–229], median overall survival was 30 months, and 3-year overall survival was 18%.

Conclusion

Ovarian metastases are less responsive to chemotherapy compared to other sites. As these “metastatic sanctuaries” often cause symptoms, surgical resection should always be considered for ovarian metastases, even in the case of associated extraovarian metastases.