Impact of tumour rupture risk on the oncological rationale for the surgical treatment choice of gastrointestinal stromal tumours.

Tumour rupture of gastrointestinal stromal tumours (GISTs) has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome. Although tumour rupture has not yet been included in the current tumor-node-metastasis classification of GISTs as a prognostic factor, it may change the natural history of a low-risk GIST to a high-risk GIST. Originally, tumour rupture was defined as the spillage or fracture of a tumour into a body cavity, but recently, new definitions have been proposed. These definitions distinguished from the prognostic point of view between the major defects of tumour integrity, which are considered tumour rupture, and the minor defects of tumour integrity, which are not considered tumour rupture. Moreover, it has been demonstrated that the risk of disease recurrence in R1 patients is largely modulated by the presence of tumour rupture. Therefore, after excluding tumour rupture, R1 may not be an unfavourable prognostic factor for GISTs. Additionally, after the standard adjuvant treatment of imatinib for GIST with rupture, a high recurrence rate persists. This review highlights the prognostic value of tumour rupture in GISTs and emphasizes the need to carefully take into account and minimize the risk of tumour rupture when choosing surgical strategies for GISTs.

Oncological outcome after lateral pelvic lymphadenectomy for low rectal carcinoma: not only an N-status matter.

Tumour deposits (TDs), novel pathological entities, should be considered when estimating the regional and systemic spread of rectal carcinoma and formulating treatment strategies. In fact, TDs may have more severe prognostic impact than lymph node positivity or the lymph node ratio. The assessment of the presence of TDs can be performed only through accurate postoperative pathological examination; however, the detection of TDs is not part of any of the procedures currently used to assess preoperative or intraoperative staging. This review aims to analyse and discuss the impact of TDs on the oncological outcome of patients who undergo surgery for advanced low rectal carcinoma. No prospective study has evaluated the impact of lateral pelvic TDs on oncological outcomes following total mesorectal excision with lateral pelvic lymphadenectomy. Although adequate total mesorectal excision allows for the excision of intramesorectal TDs, lateral pelvic lymph node dissection cannot guarantee the removal of lateral pelvic TDs; moreover, it remains to be determined whether surgical excision of lateral pelvic TDs can impact long-term outcomes. However, the identification of lateral pelvic TDs strengthens the 'staging effect' and limits the 'therapeutic effect' of lateral pelvic lymphadenectomy, supporting the rationale for the use of neoadjuvant chemoradiotherapy for rectal cancer. When evaluating the oncological outcomes after total mesorectal excision with lateral pelvic lymphadenectomy, the impact of lateral pelvic TDs should be considered.

Total mesopancreas excision is the better staging tool of the mesopancreas in pancreatic head carcinoma.

Preoperative imaging staging based on tumor, node, metastasis classification cannot be effective to avoid R1 resection because only further improvements in imaging technologies will allow the precise assessment of perineural and lymphatic invasion and the occurrence of microscopic tumour deposits in the mesopancreas. However, waiting for further improvements in imaging technologies, total mesopancreas excision remains the only tool able to precisely assess mesopancreatic resection margin status, maximize the guarantee of radicality in cases of negative (R0) mesopancreatic resection margins, and stage the mesopancreas.

Paraaortic dissection in "total mesopancreas excision" and "mesopancreas-first resection" pancreaticoduodenectomies for pancreatic cancer: Useless, optional, or necessary?A systematic review.

The mesopancreas does not have well-defined boundaries but is continuous and connected through its components with the paraaortic area. The mesopancreatic resection margin has been indicated as the primary site for R1 resection after PD in pancreatic head cancer and total mesopancreas excision has been proposed to achieve adequate retropancreatic margin clearance and to minimize the likelihood of R1 resection. However, the anatomy of the mesopancreas requires extended dissection of the paraaortic area to maximize posterior clearance. The artery-first surgical approach has been developed to increase local radicality at the mesopancreatic resection margin. During PD, the artery-first approach begins with dissection of the connective tissues around the SMA. However, the concept of the mesopancreas as a boundless structure that includes circumferential tissues around the SMA, SMV, and paraaortic tissue highlights the need to shift from artery-first PD to mesopancreas-first PD to reduce the risk of R1 resection. From this perspective the "artery-first" approach, which allows for the avoidance of R2 resection risk, should be integrated into the "mesopancreas-first" approach to improve the R0 resection rate. In total mesopancreas excision and mesopancreas-first pancreaticoduodenectomies, the inclusion of the paraaortic area and circumferential area around the SMA in the resection field is necessary to control the tumour spread along the mesopancreatic resection margin rather than to control or stage the spread in the nodal basin.

Beyond T, N and M: The impact of tumor deposits on the staging and treatment of colorectal and gastric carcinoma.

This review aims to describe the results of the most recent studies on the prognostic value of TDs and highlight the impact of TDs on the staging and treatment of colorectal and gastric carcinoma. For colorectal carcinoma TDs have an adverse prognostic effect that is at least similar to that of positive regional lymph nodes. However, support is growing in favor of including of TDs in the M category, rather than the N or T categories of the TNM classification. Moreover, TDs seem to have an adverse effect on outcomes not only in patients without lymph node involvement but also in patients with nodal involvement. Although the prognostic impact of TDs in gastric cancer appears to be undeniable, the actual prognostic determinants of TDs, particularly in relation to the number, size and histological types, remain to be established. Although the 7th and 8th Edition of the TNM classification of colorectal and gastric carcinoma includes TDs in the N category, no current procedures or methods to assess preoperative or intraoperative N-status allow TD detection. After neoadjuvant treatment for advanced rectal carcinoma, the presence of TDs may indicate incomplete eradication of the main tumor and not discontinuous tumor foci. TDs have an undeniable prognostic impact but no algorithm of staging and strategy of treatment has been conformed to this prognostic factor to overcome the classical T,N, and M prognostic categories. Staging and treatment of colorectal and gastric cancers should be reconsidered in light of the emerging prognostic value of TDs.

The "meso" of the rectum and the "meso" of the pancreas: similar terms but distinct concepts in surgical oncology.

A correspondence between the "meso" of the rectum and of the pancreas has recently been reported. Here we highlight the differences between mesorectum and mesopancreas. Based on anatomical findings from a series of 89 consecutive pancreaticoduodenectomies and 71 consecutive total mesorectal excisions, we observed that in contrast to the mesorectum, the mesopancreas did not have well-defined anatomic boundaries and was continuous and connected through its components with the para-aortic area. In rectal cancer, tumor deposits and nodal involvement could be confined to the mesorectum (i.e., within the mesorectal fascia), whereas in pancreatic carcinoma, tumor deposits and nodal metastases occurred in the boundless mesopancreatic area. Total mesorectal excision was made en bloc with the rectum by dissecting along the mesorectal fascia; this was not the case for mesopancreatic excision since anatomical demarcation of the mesopancreas did not exist. Moreover, the growth pattern of pancreatic cancer showed greater dispersion, which was more prominent at the invasive front of the tumor and could potentially affect the status of the resection margin. These findings indicate that the mesorectum and mesopancreas are completely distinct from the pathological, surgical, and oncological standpoints.

Mesopancreas: A boundless structure, namely the rationale for dissection of the paraaortic area in pancreaticoduodenectomy for pancreatic head carcinoma.

This review highlights the rationale for dissection of the 16a2 and 16b1 paraaortic area during pancreaticoduodenectomy (PD) for carcinoma of the head of the pancreas. Recent advances in surgical anatomy of the mesopancreas indicate that the retropancreatic area is not a single entity with well defined boundaries but an anatomical site of embryological fusion of peritoneal layers, and that continuity exists between the neuro lymphovascular adipose tissues of the retropancreatic and paraaortic areas. Recent advances in surgical pathology and oncology indicate that, in pancreatic head carcinoma, the mesopancreatic resection margin is the primary site for R1 resection, and that epithelial-mesenchymal transition-related processes involved in tumor progression may impact on the prevalence of R1 resection or local recurrence rates after R0 surgery. These concepts imply that mesopancreas resection during PD for pancreatic head carcinoma should be extended to the paraaortic area in order to maximize retropancreatic clearance and minimize the likelihood of an R1 resection or the persistence of residual tumor cells after R0 resection. In PD for pancreatic head carcinoma, the rationale for dissection of the paraaortic area is to control the spread of the tumor cells along the mesopancreatic resection margin, rather than to control or stage the nodal spread. Although mesopancreatic resection cannot be considered "complete" or "en bloc", it should be "extended as far as possible" or be "maximal", including dissection of 16a2 and 16b1 paraaortic areas.

Effect of surgery on pancreatic tumor-dependent lymphocyte asset: modulation of natural killer cell frequency and cytotoxic function.

OBJECTIVES: Tumor burden and invasiveness establish a microenvironment that surgery could alter. This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy. METHODS: Lymphocyte frequency and natural cytotoxicity were evaluated by flow cytometry and in vitro assay on peripheral blood from initial and advanced-stage pancreatic cancer patients before (BS), at day 7 (PS7), and at day 30 (PS30) after surgery. RESULTS: An increase in natural killer (NK) cells and the diminution of B-cells occurred at PS30, whereas cytotoxicity decreased at PS7. The positive correlation between NK frequency and cytotoxicity at BS and PS7 revealed an altered NK behavior. The elevation of NK cell frequency at PS30, an initial defect in CD56bright NK, and the aberrant correlation between NK frequency and cytotoxicity remained significant in advanced-stage patients, whereas the diminution of NK cytotoxicity only affected initial stage patients. CONCLUSIONS: The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.

Tumor rupture during surgery for gastrointestinal stromal tumors: pay attention!

In a recently published letter to the editor, we debated the proposal by Coccolini et al to treat gastrointestinal stromal tumors (GISTs) of the esophagogastric junction with enucleation and, if indicated, adjuvant therapy. We highlighted that, because the prognostic impact of a T1 high-mitotic rate esophageal GIST is worse than that of a T1 high-mitotic rate gastric GIST, enucleation may not be adequate surgery for esophagogastric GISTs with a high mitotic rate. In rebuttal, Coccolini et al pointed out the possible bias in assessment of the mitotic rates due to the lack of standardized methods and underlined that the site and features of the tumor need to be carefully considered in evaluation of the risk-benefit balance. Here we confirm that, apart from the problematic issue of mitotic counting, enucleation should not be indicated for GISTs at any site to reduce the risk of tumor rupture, which has been recently considered to be an unfavorable prognostic factor, and to avoid microscopic residual tumor.

Digestive cancer surgery in the era of sentinel node and epithelial-mesenchymal transition.

Lymph node involvement is one of the most important prognostic indicators of carcinoma of the digestive tract. Although the therapeutic impact of lymphadenectomy has not been proven and the number of retrieved nodes cannot be considered a measure of successful cancer surgery, an adequate lymph node count should be guaranteed to accurately assess the N-stage through the number of involved nodes, lymph node ratio, number of negative nodes, ratio of negative to positive nodes, and log odds, i.e., the log of the ratio between the number of positive lymph nodes and the number of negative lymph nodes in digestive carcinomas. As lymphadenectomy is not without complications, sentinel node mapping has been used as the rational procedure to select patients with early digestive carcinoma in whom nodal dissection may be omitted or a more limited nodal dissection may be preferred. However, due to anatomical and technical issues, sentinel node mapping and nodal basin dissection are not yet the standard of care in early digestive cancer. Moreover, in light of the biological, prognostic and therapeutic impact of tumor budding and tumor deposits, two epithelial-mesenchymal transition-related phenomena that are involved in tumor progression, the role of staging and surgical procedures in digestive carcinomas could be redefined.

Does antecolic reconstruction decrease delayed gastric emptying after pancreatoduodenectomy?

Delayed gastric emptying (DGE) is a frequent complication after pylorus-preserving pancreatoduodenectomy (PpPD). Kawai and colleagues proposed pylorus-resecting pancreatoduodenectomy (PrPD) with antecolic gastrojejunal anastomosis to obviate DGE occurring after PpPD. Here we debate the reported differences in the prevalence of DGE in antecolic and retrocolic gastro/duodeno-jejunostomies after PrPD and PpPD, respectively. We concluded that the route of the gastro/duodeno-jejunal anastomosis with respect to the transverse colon; i.e., antecolic route or retrocolic route, is not responsible for the differences in prevalence of DGE after pancreatoduodenectomy (PD) and that the impact of the reconstructive method on DGE is related mostly to the angulation or torsion of the gastro/duodeno-jejunostomy. We report a prevalence of 8.9% grade A DGE and 1.1% grade C DGE in a series of 89 subtotal stomach-preserving PDs with Roux-en Y retrocolic reconstruction with anastomosis of the isolated Roux limb to the stomach and single Roux limb to both the pancreatic stump and hepatic duct. Retrocolic anastomosis of the isolated first jejunal loop to the gastric remnant allows outflow of the gastric contents by gravity through a "straight route".

Pancreaticojejuno anastomosis after pancreaticoduodenectomy: brief pathophysiological considerations for a rational surgical choice.

Introduction. The best pancreatic anastomosis technique after pancreaticoduodenectomy (PD) is still debated. Pancreatic fistula (PF) is the most important complication but is also related to postoperative bleedings and pancreatic remnant involution. We support pancreaticojejuno anastomosis (PJ) advantages describing our technique with brief technical considerations. Materials and Methods. 89 consecutive patients underwent PD with suprapyloric gastric resection and double loop reconstruction. Pancreaticojejunal end-to-end anastomosis was done by simple invagination with a single layer of interrupted pledget-supported Ticron stitches. Results. Pancreatic fistula occurred in seven patients (7.8%): six cases of grade A fistula resolved spontaneously, and in only one case of grade B fistula percutaneous drainage was necessary. Postoperative hemorrhage occurred in only two (2.2%) of 89 patients. Conclusion. Pancreaticojejunostomy with minor changes in anastomotic techniques can contribute to improvement of the outcome of Roux-en-Y reconstruction regarding PF and other related complications. The particular reconstruction reported seems also to preserve the pancreatic exocrine function.

Double inferior vena cava does not complicate para-aortic nodal dissection for the treatment of pancreatic carcinoma.

Duplication of the inferior vena cava (IVC) involves large veins on both sides of the aorta that join anteriorly at the level of the renal arteries to become the suprarenal IVC. We report CT scan and intraoperative images of a patient with duplication of the IVC who underwent pancreaticoduodenectomy with para-aortic lymphadenectomy for carcinoma of the pancreatic head: nodal dissection along the left caval vein was not carried out. The anatomical background of the lymphatic flow to the para-aortic lymph nodes and the theoretic basis for lymph node dissection of the para-aortic area in cases of double IVC are highlighted. Lymphadenectomy along the left caval vein is not necessary in patients with double IVC who undergo pancreaticoduodenectomy with extended lymphadenectomy for carcinoma of the pancreatic head in the absence of preoperative appearance of para-aortic disease.