D.J. Grunhagen

Long-term results of the "liver first" approach in patients with locally advanced rectal cancer and synchronous liver metastases

BACKGROUND: There are no reports available on the long-term outcome of patients with the “liver first” approach. OBJECTIVES: The aim of this study was to present the long-term results of the “liver first” approach in our center. DESIGN: This study is a retrospective analysis. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Patients from May 2003 to March 2009 were included. INTERVENTIONS: Patients with locally advanced rectal cancer and synchronous liver metastases were first treated for their liver metastases. If the treatment was successful, patients underwent neoadjuvant chemoradiotherapy and surgery for the rectal cancer. If metastases could not be resected, resection of the rectal primary was not routinely performed. MAIN OUTCOME MEASURES: The primary outcome measured was long-term results of the “liver first” approach. RESULTS: Of the 42 patients included (median age, 61 years), all but one (98%) started with neoadjuvant chemotherapy. In total, 31 (74%) patients completed the “liver first” approach. In 11 patients, curative therapy was not possible because of unresectable metastases; in 10 of these patients (91%), the primary tumor was not resected. LIMITATIONS: This study was limited because it was a retrospective analysis without a control group. CONCLUSIONS: By applying the “liver first” approach, the majority of this group of patients (74%) could undergo curative treatment of both metastatic and primary disease in combination with optimal neoadjuvant therapy. This strategy may avoid unnecessary rectal surgery in patients with incurable metastatic disease. In this selected patient group, long-term survival may be achieved with a 5-year survival rate of 67%.

Laparoscopic‐monitored colonoscopic polypectomy: a multimodality method to avoid segmental colon resection

Aimu2002 In some patients with adenoma, snare polypectomy may be technically impossible owing to angulation of the colon or after previous surgery. This may result in a segmental colonic resection, if malignant invasion is thought to be likely. Laparoscopic mobilization of the colon to enable a simultaneous colonoscopy can avoid this difficulty.

Multicenter Observational Study of Adhesion Formation After Open-and Laparoscopic Surgery for Colorectal Cancer

Objective: The aim of this study was to compare adhesion formation after laparoscopic and open colorectal cancer resection. Summary of Background Data: After colorectal surgery, most patients develop adhesions, with a high burden of complications. Laparoscopy seems to reduce adhesion formation, but evidence is poor. Trials comparing open- and laparoscopic colorectal surgery have never assessed adhesion formation. Methods: Data on adhesions were gathered during resection of colorectal liver metastases. Incidence of adhesions adjacent to the original incision was compared between patients with previous laparoscopic- and open colorectal resection. Secondary outcomes were incidence of any adhesions, extent and severity of adhesions, and morbidity related to adhesions or adhesiolysis. Results: Between March 2013 and December 2015, 151 patients were included. Ninety patients (59.6%) underwent open colorectal resection and 61 patients (40.4%) received laparoscopic colorectal resection. Adhesions to the incision were present in 78.9% after open and 37.7% after laparoscopic resection (P < 0.001). The incidence of abdominal wall adhesions and of any adhesion was significantly higher after open resection; the incidence of visceral adhesions did not significantly differ. The extent of abdominal wall and visceral adhesions and the median highest Zühlke score at the incision were significantly higher after open resection. There were no differences in incidence of small bowel obstruction during the interval between the colorectal and liver operations, the incidence of serious adverse events, and length of stay after liver surgery. Conclusion: Laparoscopic colorectal cancer resection is associated with a lower incidence, extent, and severity of adhesions to parietal surfaces. Laparoscopy does not reduce the incidence of visceral adhesions.

Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases: Can the Extent of Surgery be Safely Minimized?

BackgroundPatients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient.AimThe aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future.MethodsThis study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992–2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT]xa0±xa0positron emission tomography [PET], or PETxa0−xa0low-dose CT).ResultsMedian age was 57xa0years, 54xa0% of patients were female, and median follow-up was 21xa0months (interquartile range [IQR] 11–46xa0months). Median Breslow thickness was 2.10xa0mm (IQR 1.40–3.40xa0mm), and 26xa0% of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35xa0% of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1–2] vs. 3 [IQR 1–4] for positive deep pelvic nodes; pxa0<xa00.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10–0.25) vs. 0.33 (IQR 0.14–0.54); pxa0<xa00.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84xa0% of patients.ConclusionsPatients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

Local excision of rectal cancer afterchemoradiation: feasibility depends on the primary stage

Dear Editor, n nIn the Netherlands, the standard treatment for T2–3 rectal cancer is a short-course preoperative radiotherapy (5u2009×u20095 Gy) followed by total mesorectal excision (TME). The Dutch TME trial proved that the addition of preoperative radiotherapy to surgery decreased the 5-year local recurrence rate from 11% to 6%. For patients with locally advanced rectal cancer, a long course of preoperative chemoradiation therapy is usually performed (25u2009×u20092 Gy). This treatment is based on trials by Bosset and Gerard that demonstrated that the addition of 5-fluorouracil yielded higher response rates and lower local recurrence rates. n nThe introduction of neoadjuvant chemoradiation therapy for locally advanced rectal cancer has also introduced a dilemma. In approximately 10–15% of patients, a pathological complete response is seen in the resection specimen. For these patients, a wait-and-see policy may be beneficial, with regard to both survival and quality of life. However, preoperative staging of rectal carcinoma after chemoradiation therapy has proven to be inaccurate. Both Hiotis and Zmora showed that only 25–33% of rectal cancers that had a complete clinical response indeed had a complete pathological response. Many surgeons therefore choose to remove the tumour area by local excision to confirm the response to chemoradiation therapy pathologically. In a study by Guerrieri, 196 rectal cancer patients were treated by neoadjuvant radiation therapy and local excision alone. Excellent results were reported, even though these surgeons never performed salvage TME, irrespective of the pathological T-stage. n nHereby, we present the case of a patient with a clinical T3–4N0 rectal cancer and a clinical complete response to chemoradiation therapy that was treated by local excision. This 74-year-old woman was seen in the outpatient department with complaints of rectal blood loss and residual stool. Rectal examination revealed a ventral tumour, located just above the anal verge. The tumour appeared mobile, and the vaginal mucosa was intact. At colonoscopy, a biopsy was taken, revealing a moderately differentiated adenocarcinoma. A magnetic resonance imaging (MRI) of the pelvis showed rectal cancer, extending 5–10xa0cm from the anal verge. The carcinoma invaded the subserosa and perirectal tissue. Ingrowth in the vaginal wall could not be ruled out. There was no lymphadenopathy, and no distant metastases were found after computed tomography of the abdomen and thorax. The clinical tumour, node, and metastasis (TNM) stage was cT3-4N0M0. n nThe patient was scheduled for neoadjuvant chemoradiation therapy (25u2009×u20092 Gy + capecitabine 2 bid 825xa0mg). Six weeks after chemoradiation, the response was evaluated by rectal examination, MRI of the pelvis, endoanal ultrasound, and rectoscopy. There appeared to be a complete response, without lymphadenopathy. Only a small ulcer remained, located centrally in the area where the tumour was located. Again, no distant metastases were seen. After discussing the results with the patient, she was scheduled for local excision of the tumour area by TEM 10xa0weeks after completion of chemoradiation therapy, although the tumour area had not been tattooed prior to chemoradiation therapy. The central ulcer with surrounding fibrosis was excised with a margin of 1xa0cm macroscopically normal mucosa, resulting in a specimen with an area of 6u2009×u20095xa0cm. Standardised pathology revealed a moderately differentiated adenocarcinoma, infiltrating the muscularis propria. The area of the ulcer and surrounding fibrosis was 3u2009×u20092.5xa0cm. The margins were complete with a minimal distance of 4xa0mm, resulting in a R0 ypT2Nx resection. n nA salvage TME was proposed, with which the patient agreed. Since she experienced soiling before treatment, we decided to perform an intersphincteric rectal amputation rather than making a low anastomosis. The procedure took place 18xa0weeks after the completion of chemoradiation therapy. The rectum was found to be fixed to the posterior vagina. The posterior vaginal wall was partially excised, and the defect closed with sutures. n nThe pathology report revealed extensive radiation effects and scar tissue. Notably, a focus of vital adenocarcinoma was found. It was located in the perirectal fat and had a diameter of 2xa0mm. Four perirectal lymph nodes without tumour were found. The margins were complete. As a consequence, the pathological TNM stage after chemoradiation therapy was changed to ypT3N0 rectal cancer. n nAlthough this 74-year-old patient had a clinical complete response to neoadjuvant chemoradiation, pathological examination of the specimen revealed a T2 rectal cancer with complete margins after local excision. Notably, the salvage TME specimen contained a viable cancer cell nest at a deeper level, changing the pathological T stage to T3 rectal cancer. To our knowledge, no similar case has been reported. We argue that the local excision of rectal cancer after chemoradiation carries the risk of leaving behind viable cancer cell nests. This is probably caused by a scattered regression pattern of rectal cancer in response to chemoradiation therapy. With regard to local recurrence, it is often thought that the local recurrence after a local excision is caused by a concurrent lymph node disease. However, failure to remove viable cancer cell nests is likely to play a role in local recurrence as well. Because resection margins may be complete, these viable cancer cell nests can easily go unnoticed. n nApart from increasing the risk of local recurrence, the remaining viable cancer cell nests can also result in pathological understaging, as was the case in this patient. The pathological T stage after chemoradiation therapy and local excision of rectal cancer determines the risk of local recurrence and lymph node involvement. It is the basis on which surgeons decide to either adopt an observational strategy or proceed with a salvage TME. Borschitz and Bujko reported that local excision of ypT0 rectal cancer is associated with a 0% local recurrence rate and a 5% risk of lymph node disease. YpT1 has a 2% local recurrence rate and an 8% risk of lymph node disease. Therefore, ypT0 and ypT1 are often seen as candidates for an observational strategy. On the other hand, ypT2 is associated with a 7% local recurrence rate and a 28% risk of lymph node disease. YpT3 is associated with a 21% local recurrence rate and a 55% risk of lymph node disease. Local excision of ypT2 or ypT3 rectal cancer is therefore usually followed by a salvage TME. It follows that an accurate pathological staging after local excision is of the utmost importance. n nTo avoid this kind of irradical resection, local recurrence, and pathological understaging after local excision of rectal cancer, it is imperative that all tissues that were primarily invaded by the rectal cancer are removed. The circumferential mucosal margins of the tumour should be marked by tattooing the edges of the tumour prior to the start of neoadjuvant chemoradiation therapy. The deep margins cannot be marked. This means that when the primary T stage was cT3, a complete resection of the mesorectal layer deep to the tattooed tumour area is mandatory. Moreover, the accuracy of preoperative assessment of the depth of invasion is limited. Therefore, mesorectal excision may also be advisable for cT2 rectal cancer. Although mesorectal excision by local techniques is not a standard procedure, it is feasible, both by TEM and other endoscopic techniques. It is important to realise that local excision of all tissues that were primarily invaded by rectal cancer is not feasible if the primary stage was T4. Moreover, local mesorectal excision does not result in an adequate lymphadenectomy. n nDear Editor, n nWe agree that the results of local excision of rectal cancer after chemoradiation therapy are promising. However, the case we reported in this letter proves that an accurate pathological staging can only be achieved if all tissues that were primarily invaded by the tumour are excised. Therefore, circumferential margins of the tumour should be tattooed prior to chemoradiation therapy, and in patients with cT3 rectal cancer, a complete excision of the mesorectal tissue deep to the tumour area is mandatory. Patients with cT4 rectal cancer or lymph node-positive disease are not good candidates for local excision.

Timing of completion lymphadenectomy after positive sentinel node biopsy in patients with melanoma

Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease‐free survival (DFS) and/or melanoma‐specific survival (MSS).

Pigmentation in the sentinel node correlates with increased sentinel node tumor burden in melanoma patients.

The prognosis of sentinel node (SN)-positive melanoma patients is predicted by a number of characteristics such as size and site of the metastases in the SN. The pathway and prognosis of strong pigmentation of melanoma metastases in the SN is unclear. The aim of this study is to evaluate the role of pigmentation and growth pattern of metastases in the SN with respect to survival. A total of 389 patients underwent an SN procedure (1997–2011). Ninety-five patients had a positive SN and material from 75 patients was available for review. The median follow-up time was 75 months (range 6–164). Pigmentation was scored from 0 to 2 using the following scale: 0=absent, 1=slight, and 2=strong. Growth pattern was scored as either eccentric (1) or infiltrative (2). SN tumor burden was measured according to the Rotterdam criteria. The primary melanoma had a median Breslow thickness of 2.90 mm (0.8–12.00 mm). Ulceration was present in 34 patients (45.3%). There was a median SN tumor burden of 0.5 mm (0.05–7.00 mm). In a total of 75 patients, 59 patients (79%) had no pigmentation, 13 patients (17%) had slight pigmentation, and three patients (4%) had strong pigmentation in the SN. Because of the small numbers, the classification was modified to either absent 59 (79%) or present 16 (21%) pigmentation, respectively. The SN tumor burden was significantly higher (P=0.031) for patients with pigmentation. Patients with pigmentation had a 5-year melanoma-specific survival (MSS) of 47% and a 10-year MSS of 33%. Patients without pigmentation had a 5-year MSS of 70% and a 10-year MSS of 59% (P=0.06). There was no difference in MSS for patients with an eccentric or an infiltrative growth pattern, nor did it correlate with other prognostic factors. Multivariate analysis for MSS showed five significant factors associated with worse prognosis: male sex (P=0.036), nodular melanoma (P=0.001), truncal site (P=0.0001), SN tumor burden more than 1.0 mm (P=0.022), and positive completion lymph node dissection (P=0.004). The 5-year MSS for SN tumor burden is 94% for 0.1 mm or less, 66% for 0.1–1.0 mm, and 41% for more than >1.0 mm (P<0.001). The 10-year MSS for SN tumor burden is, respectively, 94, 51, and 35% (P<0.001). This preliminary exploratory retrospective study showed that pigmentation within the SN seems to correlate with increased SN tumor burden.

Surgical and medical management of small bowel gastrointestinal stromal tumors: a report of the Dutch GIST registry

BACKGROUNDnA cohort of 201 patients with small bowel gastrointestinal stromal tumors (GIST) treated between January 1st, 2009 and December 31st, 2016 in five GIST expertise centers in the Netherlands was analyzed. Goal of this study was to describe the clinical, surgical and pathological characteristics of this rare subpopulation of GIST patients, registered in the Dutch GIST registry.nnnMETHODSnClinical outcomes and risk factors of patients with small bowel GIST who underwent surgery or treated with systemic therapy were analyzed. A classification was made based on disease status at diagnosis (localized vs. metastasized).nnnRESULTSn201 patients with small bowel GIST were registered of which 138 patients (69%) were diagnosed with localized disease and 63 patients (31%) with metastatic disease. Approximately 19% of the patients had emergency surgery, and in 22% GIST was an accidental finding. In patients with high risk localized disease, recurrence occurred less often in patients who received adjuvant treatment (4/32) compared to patients who did not (20/31, pu202f<u202f0.01). Disease progression during palliative imatinib treatment occurred in 23 patients (28%) after a median of 20.7 (range 1.8-47.1) months. Ongoing response was established in 52/82 patients on first line palliative treatment with imatinib after a median treatment time of 30.6 (range 2.5-155.3) months.nnnCONCLUSIONnPatients with small-bowel GIST more frequently present with metastatic disease when compared to patients with gastric GIST in literature. We advocate for Prospective registration of these patients and investigate the use of surgery in patients with limited metastatic disease.

Isolated Limb Perfusion for Melanoma in Transit Metastases

The treatment of melanoma in transit metastases can vary widely and is dependent on the size and number of lesions. When many, large lesions exist, isolated limb perfusion (ILP) can be used as an attractive treatment option with high response rates. We review here the various methods of treatment for melanoma in transit metastases, with a focus on ILP. Indications and results are discussed, and the extra value of tumour necrosis factor (TNF) is evaluated. ILP with melphalan results in complete response rates of 40 to 82% (54% in a large retrospective metaanalysis). The addition of TNF can improve these complete response rates (59–85%), and although no data from randomized controlled trials are available, TNF seems of particular value in large, bulky lesions or in patients with recurrent disease after previous ILP. TNF-based ILP has earned a permanent place in the treatment of patients with melanoma it transit metastases. In patients with a high tumor burden, TNF-based ILP is the most efficacious procedure to obtain local control and achieve limb salvage.