Effective generation of tumor-infiltrating lymphocyte products from metastatic non-small-cell lung cancer (NSCLC) lesions irrespective of location and previous treatments.

Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Because current treatment regimens show limited success rates, alternative therapeutic approaches are needed. We recently showed that treatment-naïve, stage I/II primary NSCLC tumors contain a high percentage of tumor-reactive T cells, and that these tumor-reactive T cells can be effectively expanded and used for the generation of autologous tumor-infiltrating T cell (TIL) therapy. Whether these promising findings also hold true for metastatic lesions is unknown yet critical for translation into the clinic. Materials and methods: We studied the lymphocyte composition using flow cytometry from 27 metastatic NSCLC lesions obtained from different locations and from patients with different histories of treatment regimens. We determined the expansion capacity of TILs with the clinically approved protocol, and measured their capacity to produce the key pro-inflammatory cytokines interferon-γ, tumor necrosis factor and interleukin 2 and to express CD137 upon co-culture of expanded TILs with the autologous tumor digest. Results: The overall number and composition of lymphocyte infiltrates from the various metastatic lesions was by and large comparable to that of early-stage primary NSCLC tumors. We effectively expanded TILs from all metastatic NSCLC lesions to numbers that were compatible with TIL transfusion, irrespective of the location of the metastasis and of the previous treatment. Importantly, 16 of 21 (76%) tested TIL products displayed antitumoral activity, and several contained polyfunctional T cells. Conclusions: Metastatic NSCLC lesions constitute a viable source for the generation of tumor-reactive TIL products for therapeutic purposes irrespective of their location and the pre-treatment regimens.

The role of surgery in the treatment of oligoprogression after systemic treatment for advanced non-small cell lung cancer.

OBJECTIVES: Patients with advanced stage non-small cell lung cancer (NSCLC) are generally considered incurable. The mainstay of treatment for these patients is systemic therapy. The addition of local treatment, including surgery, remains controversial. Oligoprogression is defined as advanced stage NSCLC with limited progression of disease after a period of prolonged disease stabilisation or after a partial or complete response on systemic therapy. In this retrospective study we evaluated outcome and survival of patients who underwent a resection for oligoprogression after systemic therapy for advanced stage NSCLC. MATERIALS AND METHODS: Patients with oligoprogression after systemic treatment for advanced NSCLC who were operated in the Antoni van Leeuwenhoek Hospital were included. Patient and treatment characteristics were collected in relation to progression free survival (PFS) and overall survival (OS). RESULTS: Between January 2015 and December 2019, 28 patients underwent surgery for an oligoprogressive lesion (primary tumor lung (n = 12), other metastatic site (n = 16)). Median age at time of resection was 60 years (39-86) and 57% were female. Postoperative complications were observed in 2 patients (7%). Progression of disease after resection of the oligoprogressive site was observed in 17 patients (61%). Median PFS was 7 months since date of resection (95% CI 6.0-25.0) and median OS was not reached. Seven patients (25%) died during follow-up. Age was predictive for OS and clinical T4 stage was predictive for PFS. M1 disease at initial presentation was predictive for better PFS compared to patients who were diagnosed with M0 disease initially. Patients who underwent resection because of oligoprogression of the primary lung tumour had a better PFS, when compared to oligoprogression of another metastastic site. CONCLUSION: Surgical resection of an oligoprogressive lesion in patients with advanced NSCLC treated with systemic treatment is feasible and might be considered in order to achieve long term survival.

Perioperative Management of Gastric Cancer Patients Treated With (Sub)Total Gastrectomy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Lessons Learned.

BACKGROUND: The PERISCOPE I study was designed to assess the safety and feasibility of (sub)total gastrectomy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and docetaxel for gastric cancer patients who have limited peritoneal dissemination. The current analysis investigated changes in perioperative management together with their impact on postoperative outcomes. METHODS: Patients with resectable gastric cancer and limited peritoneal dissemination were administered (sub)total gastrectomy, CRS, and HIPEC with oxaliplatin (460 mg/m2) and docetaxel (escalating scheme: 0, 50, 75 mg/m2). Of the 25 patients who completed the study protocol, 14 were treated in the dose-escalation cohort and 11 were treated in the expansion cohort (to optimize perioperative management). RESULTS: A significant proportion of the patients in the dose-escalation cohort (n = 7, 50%) had ileus-related complications. In this cohort, enteral nutrition was started immediately after surgery at 20 ml/h, which was increased on day 1 to meet nutritional needs. In the expansion cohort, enteral nutrition was administered at 10 ml/h until day 3, then restricted to 20 ml/h until day 6, supplemented with total parenteral nutrition to meet nutritional needs. Ileus-related complications occurred for two patients (18%) of the expansion cohort. The intensive care unit (ICU) readmission rate decreased from 50 (n = 7) to 9% (n = 1; p = 0.04). CONCLUSION: The implementation of a strict nutritional protocol during the PERISCOPE I study was associated with a decrease in postoperative complications. Based on these results, a perioperative care path was described for the gastric cancer HIPEC patients in the PERISCOPE II study.

Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results.

BACKGROUND: The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS: Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2 ). RESULTS: Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2 ) and four at dose level 3 (75 mg/m2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION: Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.

ANTECEDENTES: El papel de la cirugía citorreductora (cytoreductive surgery, CRS) combinado con la quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) en el cáncer gástrico no está definido. Este estudio fase I-II no aleatorizado de escalado de dosis fue diseñado para evaluar la seguridad y la viabilidad de HIPEC, después de la quimioterapia sistémica, en pacientes con cáncer gástrico con diseminación peritoneal limitada. Además, se exploró la máxima dosis tolerada (maximum tolerated dose, MTD) de docetaxel intraperitoneal normotérmico en combinación con una dosis fija de oxaliplatino intraperitoneal. MÉTODOS: Se incluyeron pacientes con adenocarcinoma gástrico cT3-cT4a resecable con metástasis peritoneales limitadas y/o citología peritoneal positiva. Se utilizó una técnica HIPEC abierta con 460 mg/m2 de oxaliplatino hipertérmico (30 minutos) seguido de docetaxel normotérmico (90 minutos) en dosis crecientes (0, 50, 75 mg/m2 ). RESULTADOS: Entre 2014 y 2017, se incluyeron 37 pacientes. De los 25 pacientes que completaron la totalidad del protocolo del estudio, 4 pacientes fueron tratados en el nivel de dosis 1 (0 mg/m2 de docetaxel), 6 pacientes en el nivel de dosis 2 (50 mg/m2 ) y 4 pacientes en el nivel de dosis 3 (75 mg/m2 ). En el nivel de dosis 3, se produjeron dos casos de toxicidad limitante de dosis (dose-limiting toxicities, DLTs), ambas asociadas con un íleo postoperatorio. Posteriormente, otros 11 pacientes fueron tratados con el nivel de dosis 2, y no se produjeron más DLTs. La MTD de docetaxel intraperitoneal fue de 50 mg/m2 . Se registraron efectos adversos graves en 17 de 25 pacientes. La tasa de reoperación fue del 16% (n = 4) y la mortalidad relacionada con el tratamiento fue del 8% (n = 2; ambos en el nivel de dosis 3).

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II).

BACKGROUND: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. METHODS: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3-4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. DISCUSSION: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. TRIAL REGISTRATION: clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

Surgical stress response and postoperative immune function after laparoscopy or open surgery with fast track or standard perioperative care: a randomized trial.

OBJECTIVE: To evaluate the effect of laparoscopic or open colectomy with fast track or standard perioperative care on patient's immune status and stress response after surgery. METHODS: Patients with nonmetastasized colon cancer were randomized to laparoscopic or open colectomy with fast track or standard care. Blood samples were taken preoperatively (baseline), and 1, 2, 24, and 72 hours after surgery. Systemic HLA-DR expression, C-reactive protein, interleukin-6, growth hormone, prolactin, and cortisol were analyzed. RESULTS: Nineteen patients were randomized for laparoscopy and fast track care (LFT), 23 for laparoscopy and standard care (LS), 17 for open surgery and fast track care (OFT), and 20 for open surgery and standard care (OS). Patient characteristics were comparable. Mean HLA-DR was 74.8 in the LFT group, 67.1 in the LS group, 52.8 in the OFT group, and 40.7 in the OS group. Repeated-measures 2-way analysis of variance (ANOVA) showed this can be attributed to type of surgery and not aftercare (P = 0.002). Interleukin-6 levels were highest in the OS group. Repeated-measures 2-way ANOVA showed this can be attributed to type of surgery and not aftercare (P = 0.001). C-reactive protein levels were highest in the OS group. Following repeated-measures 2-way ANOVA, this can be attributed to type of surgery and not aftercare (P = 0.022). Growth hormone was lowest in the LFT group. Following repeated-measures 2-way ANOVA, this can be attributed to type of aftercare and not to type of surgery (P = 0.033). No differences between the groups were seen regarding prolactin or cortisol. No differences in (infectious) complication rates were observed between the groups. CONCLUSIONS: This randomized trial showed that immune function of HLA-DR in patients undergoing laparoscopic surgery with fast track care remains highest. This can be attributed to type of surgery and not aftercare. These results may indicate a reason for the accelerated recovery of patients treated laparoscopically within a fast track program as described in the LAparoscopy and/or FAst track multimodal management versus standard care (LAFA-Trial) (www.trialregister.nl, protocol NTR222).

Laparoscopic versus transverse Incision right colectomy for colon carcinoma.

AIM: We investigated whether laparoscopic right colectomy has short-term and / or oncological advantages compared with transverse incision right colectomy. METHOD: Patients who underwent an elective laparoscopic right colectomy or an open right colectomy through a transverse incision at the VU University Medical Center or Zaans Medical Center from 2005 to 2009 were prospectively followed. RESULTS: Patient groups were comparable in terms of gender, body mass index and American Society of Anesthesiology classification. Patients in the transverse incision group were older (68 years vs 75 years, P = 0.07) and blood loss was greater during this procedure (60 ml vs 130 ml, P = 0.001), which cost less than the laparoscopic procedure (€6.033 vs €7.221, P = 0.03). Hospital stay for the laparoscopic group was shorter (8 days vs 9 days, P = 0.04), but laparoscopic procedures took longer (155 min vs 77 min, P < 0.001) and 8% of patients in the laparoscopic group were converted to a median laparotomy. Postoperative complications were comparable for both groups (28% vs 32%, P = 0.74), and in both groups a radical resection rate of 96% (P = 0.94) was achieved. At a median follow up of 20 months the incidence of incisional hernia was similar in both groups and no patient required additional surgery as a result. Overall survival at 60 months was 70% for the laparoscopic group and 67% for the transverse incision group (P = 0.84). CONCLUSION: There a re few clinically relevant differences between a laparoscopic right colectomy and a transverse incision right colectomy. Transverse incision right colectomy is cheaper. The study may be the first to compare these two techniques, but it is a nonrandomized trial and therefore has its limitations.

The surgical stress response and postoperative immune function after laparoscopic or conventional total mesorectal excision in rectal cancer: a randomized trial.

PURPOSE: This study evaluated differences in stress response and immunological function following laparoscopic and conventional total mesorectal excision (TME) for rectal cancer. METHODS: Patients with non-metastasized rectal cancer were prospectively randomized to open (n = 18) or laparoscopic (n = 22) TME. Blood samples were taken preoperatively (baseline), 2, 24, and 72 h following surgery. Systemic white blood cell and monocyte count, C-reactive protein, interleukin-6 (IL-6), interleukin-8 (IL-8), HLA-DR expression on monocytes, growth hormone, prolactin, and cortisol were measured. RESULTS: Forty patients with a median age of 66 years (interquartile range, 60-74 years) were included. Eighteen patients (45%) were randomized to open surgery and 22 patients (55%) to laparoscopic surgery. Patient demographics in terms of gender, age, BMI, ASA classification, localization of the tumor, and type of neoadjuvant therapy were comparable for both groups. Laparoscopic surgery resulted in a significantly better short-term preservation of postoperative immune function. HLA-DR expression on monocytes was significantly higher (64% vs 50%, P = 0.014) and IL-6 level increase was significantly lower (4.6 vs 10.8, P = 0.003) 2 h after laparoscopic surgery. No differences between the open and laparoscopic technique were observed in postoperative white blood cell count, monocyte count, C-reactive protein, IL-8, growth hormone, prolactin, and cortisol levels. CONCLUSION: Short-term postoperative immune and inflammatory functions tended to be better after laparoscopic rectal surgery. However, the differences were not consistent at all time intervals, making a definitive conclusion difficult. Better preserved inflammatory function 2 h after surgery may reflect a reduction in operative trauma when the laparoscopic technique is compared with open rectal procedures.

Systematic approach of postoperative gastric conduit complications after esophageal resection.

Complications after esophagectomy related to ischemia of the graft are dreaded. Prompt assessment of the situation is essential. The series presented describes our experience regarding the evaluation of gastric tube complications. A score is presented classifying flexible endoscopy and CT-scan findings. A retrospective analysis from the charts of 47 consecutive patients who underwent esophagectomy for cancer was conducted. Patients who underwent upper endoscopy during admittance were entered in this study. Findings on flexible endoscopy and CT scan were systematic scored. According to the findings, different attitudes were taken. Between January 2006 and December 2007, 47 patients underwent esophagectomy for cancer. Eleven (23%) out of 47 patients were suspected to have complications related to the viability of the anastomosis. Median period to deterioration was 5 days. In 3 (27%) patients, stent placement was the only intervention necessary. In 2 (18%) patients, stent placement was combined with drainage of abscesses in the upper mediastinum. Five (46%) patients required a new right thoracotomy, with drainage of mediastinal abscesses and empyema. In 2 patients a limited resection and a new cervical anastomosis with a stent was created. Mean intensive care admission and hospital admittance was 30.2 days and 67.9 days, respectively. Two patients (18%) died during hospital admittance. All cervical anastomosis required postoperative dilatation. No complications related to the use of flexible endoscopy were seen. An aggressive policy is adopted in patients deteriorating following esophagectomy. CT-scanning of the thorax and a flexible endoscopy of the gastric conduit should always be performed. Direct therapy should be adopted without delay.

Risk factors and management of presacral abscess following total mesorectal excision for rectal cancer.

INTRODUCTION: There is scant information regarding the incidence, risk factors and management of presacral abscesses following total mesorectal excision (TME) for rectal cancer. METHODS: Gender, age, body mass index (BMI), neoadjuvant radiation therapy, ASA classification, tumor size, tumor localization and fecal diversion were investigated as independent risk factors for the development of a presacral abscess. RESULTS: 261 patients were included, 26 patients (10%) developed a presacral abscess. Twenty-two patients (14.8%) with and 4 patients (3.6%) without neoadjuvant radiation therapy developed a presacral abscess (p = 0.003), respectively. Nine ASA 1 patients (5.7%), 8 ASA 2 patients (8.5%) and 3 ASA 3 patients (70%) developed a presacral abscess (p = 0.001). More presacral abscesses were observed after resection of larger tumors: 38 versus 30 mm (p = 0.041). No correlation between gender, age, BMI, tumor localization and the development of a prescaral abscess was found. Management of the presacral abscess, without overt leakage, was initially performed by drainage through the anastomosis following anterior resections and through the perineal suture line following abdominoperineal resections. CONCLUSION: Presacral abscess is a frequent (10%) complication following TME for rectal cancer. Patients in poor general condition, neoadjuvant radiation therapy and large tumors are at risks for developing a presacral abscess. Management, without overt leakage, is in our experience best executed by drainage through the anastomosis or perineal suture line.

The relationship of histological tumor regression grade (TRG) and two different time intervals to surgery following radiation therapy for locally advanced rectal cancer.

BACKGROUND: The objective of this study was to assess the effect of two different time intervals between radiation therapy and surgery for rectal cancer on the histological tumor regression grade (TRG) in the resected specimen. METHODS: Between 1995 and 2000, patients undergoing preoperative radiation therapy and TME for locally advanced (T3N0 and T3N1) mid and low rectal tumors treated in the VU University Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment (5 x 5 Gy) in the VU University medical center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6-8 weeks in the VU University Medical Center (LI group). All available histological material was reevaluated for TRG and correlated to survival. RESULTS: Sixty-seven patients were included in the present study, 28 in the LI group and 39 in the SI group. Patient gender was comparable for both groups with 21 (75%) male patients in the LI group versus 26 (67%) male patients in the SI group (p = 0.46). A T3N0 preoperative tumor stage was found in 21 (75%) patients in the LI group and in 33 (85%) patients in the SI group (p = 0.36). All tumors were histologically proven adenocarcinoma. Patients in the SI group were significantly older (67 vs. 58 years). In the LI group, a significantly more pronounced histological tumor regression was found. A complete response (TRG1), combined with a near complete histological response (TRG 2), were present in 12 patients in the LI group and in four patients in the SI group (p = 0.002). Radicality of resection was comparable for both groups. With a follow-up of over 60 months, there were no statistically significant differences between the SI and LI groups regarding local control, overall, or disease-free survival. CONCLUSION: Although histological tumor regression is significantly more pronounced following a long interval between radiation therapy and surgery, in the present study, this is not reflected in a better radical resection rate, local control or better overall and disease-free survival.

Influence of circumferential resection margin on prognosis in distal esophageal and gastroesophageal cancer approached through the transhiatal route.

We studied the influence of circumferential resection margin (CRM) involvement on survival in patients with malignancies of the distal esophagus and gastroesophageal junction. One hundred ten consecutive patients undergoing a laparoscopic or open transhiatal esophagectomy for malignancy of the distal 5 cm of the esophagus, or a Siewert I gastroesophageal junction tumor were analyzed, retrospectively. Only patients with potentially resectable tumors were included. CRM status was defined as clear or involved (microscopic tumor within 1 mm of the resection margin). Statistical analysis was done by means of univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard model. One hundred ten patients were analyzed. Sixty patients underwent open transhiatal esophagectomy, and 50 patients underwent laparoscopic transhiatal esophagectomy. There were 6 (5%) T(1), 18 (16%) T(2), and 86 (89%) T(3) tumors. CRM was clear in 68 (62%) patients and involved in 42 (38%) patients. Median survival in these groups was 50 vs. 20 months (P = 0.000). Since CRM involvement was only seen in T(3) tumors, this group was analyzed in detail. Median survival in the T(3)CRM(-) and T(3)CRM(+) group was 33 vs. 19 months (P = 0.004). For T(3)N(0) tumors, median survival in CRM(-) and CRM(+) was 40 and 22 months, respectively (P = 0.036). Median survival for T(3)N(1) tumors in CRM(-) and CRM(+) was 22 and 13 months, respectively (P = 0.049). Involvement of the circumferential resection margin was found to be an independent prognostic factor on survival in our study. It predicts a poor prognosis in patients with potentially resectable malignancies of the distal 5 cm of the esophagus and Siewert I adenocarcinomas of the gastro esophageal junction.

Morbidity and complications of protective loop ileostomy.

OBJECTIVE: The creation of a loop ileostomy is considered suitable to protect a distal anastomosis in colorectal surgery. This technique is, however, associated with failure, complications and even mortality. The aim of this study was to quantify retrospectively the morbidity associated with an ileostomy and its subsequent closure. METHOD: One hundred and nineteen patients with a temporary loop ileostomy, created between January 2000 and July 2007 were retrospectively analysed from a review of patient records. RESULTS: All ileostomies were closed after a median period of 106 days (interquartile range: 69-174 days). Stoma-related morbidity occurred in 23 (19%) patients. After ileostomy closure, 16 major complications were seen in 14 (12%) patients and 43 minor complications occurred in 25 (21%) patients. Sixty-three patients (53%) had neither stoma-related morbidity or peri- or postoperative complications after stoma closure. CONCLUSION: Protective loop ileostomy was found to be associated with a high morbidity. This raises the question of the mode of identifying the specific patients with a low anastomosis who should be provided an ileostomy for protection, set against the potential complications of the formation and closure of the ileostomy.

Technical difficulty grade score for the laparoscopic approach of rectal cancer: a single institution pilot study.

INTRODUCTION: We aimed to categorize laparoscopic rectal resections according to technical difficulty to standardize learning purposes and stratify results, making future studies more comparable. MATERIALS AND METHODS: Fifty patients undergoing a laparoscopic total mesorectal excision were prospectively followed. Four preoperatively known facts (gender, body mass index (BMI), tumor localization, and preoperative radiation therapy) were compared to four operative outcomes (operation time, blood loss, a visual analogue score (VAS) for difficulty rewarded by the surgeon, and oncological radicality of the procedure). RESULTS: Operating time for male and female patients was 257 vs. 245 min (P=0.229), blood loss was 300 vs. 300 ml (P=0.309), the VAS was 8 vs. 6 (P<0.001), and radicality was 93% vs. 91% (P=0.806). Operating time was 215, 250, and 305 min for high, mid, and low tumors (Spearman -0.44; P=0.02), respectively. Blood loss was 105, 300, and 600 ml (Spearman -0.38; P=0.01). Lower tumors were rewarded a higher VAS (Spearman -0.57; P<0.001) and were less often radically resected (Spearman 0.32; P=0.026). Operating time for irradiated and nonirradiated patients was 277 vs. 225 min (P=0.008), blood loss was 500 vs. 150 ml (P=0.006), the VAS was 7 vs. 5 (P<0.001), and radicality was 79% vs. 100% (P=0.046). Operating time was 240 min for BMI 25-30 and 253 min for BMI>30 (Spearman 0.13; P=0.391). Blood loss was 150 ml for BMI 25-30 and 500 ml for BMI>30 (Spearman 0.38; P=0.01). Higher BMIs were rewarded a higher VAS (Spearman 0.06; P=0.704). BMI had no correlation to radicality of the procedure (Spearman -0.12; P=0.402). There was an association between technical difficulty score and operation time (P=0.007), blood loss (P<0.001), VAS (P<0.001), and radicality of surgery (P=0.043). CONCLUSION: Laparoscopic surgery in male, irradiated, and obese patients with lower tumors seemed more difficult. A categorization according to technical difficulty, to preoperatively predict difficulty of the procedure, was found feasible.

Laparoscopic versus open total mesorectal excision: a comparative study on short-term outcomes. A single-institution experience regarding anterior resections and abdominoperineal resections.

BACKGROUND: Laparoscopic total mesorectal excision (TME) is being used in rectal cancer more frequently. The aim of this study was to analyze the differences in short-term outcomes between open and laparoscopic TME. METHODS: In this nonrandomized consecutive study, the short-term outcomes of 100 patients undergoing TME for proven rectal cancer were analyzed. RESULTS: Two groups of 50 patients underwent an open or laparoscopic TME for rectal cancer. Both groups were comparable. Laparoscopic surgery took longer to perform (250 vs. 197.5 min, p < 0.01), but was accompanied by less blood loss (350 vs. 800 ml, p < 0.01). Enteric function recovered sooner after laparoscopy. The numbers of major and minor complications were comparable between both groups, although fewer patients had major complications in the laparoscopic group (6 vs. 15 patients, p = 0.03). Hospital stay was shorter for patients who underwent a laparoscopic abdominoperineal resection (10 vs. 12 days, p = 0.04). Median follow-up was 17 months for the laparoscopic group and 22 months for the open group. Survival analyses between the groups showed no statistical difference in disease-free and overall survival. CONCLUSION: This study shows that laparoscopic TME for rectal cancer is a safe and feasible technique with some short-term benefits over open TME.

Preoperative polyethylene glycol versus a single enema in elective bowel surgery.

BACKGROUND: At the beginning of 2004, a large Dutch randomized study comparing mechanical bowel preparation with a single preoperative enema reported no differences in anastomotic leakage rates, septic complications, or mortality. On the basis of this study, this institution abandoned the routine practice of bowel preparation with polyethylene glycol and introduced a single preoperative enema. METHODS: A consecutive series of 78 patients undergoing elective colorectal surgery with mechanical bowel preparation using polyethylene glycol (PG group) was compared to a consecutive series of 71 patients with a single preoperative enema (SE group). The PG group was operated between June 2003 and December 2004, the SE group between January 2005 and January 2006. Mortality, anastomotic leakage, and infectious and noninfectious complications were compared. RESULTS: Mortality, anastomotic leakage, frequency of reoperations, and hospital stay were comparable for both groups. The overall postoperative morbidity was significantly higher in the SE group (26 vs. 9, p = 0.003). Specifically, the incidence of wound infections was significantly higher in the SE group (7 vs. 1, p = 0.041). Furthermore, a trend was observed in the incidence of intra-abdominal infections which was higher in the SE group (8 vs. 2, p = 0.070). Also a trend toward more extra-abdominal infectious complications was seen in the SE group (11 vs. 4, p = 0.086). CONCLUSIONS: Based on both the conflicting data currently available from different randomized studies and our results, the preoperative bowel preparation protocol in our institution has been changed. All left-sided colonic resections, in patients who can tolerate mechanical bowel preparation, are prepared with polyethylene glycol.

Preoperative radiation therapy for locally advanced rectal cancer: a comparison between two different time intervals to surgery.

BACKGROUND: Although it is now considered a standard treatment to irradiate an advanced mid or low rectal tumor before surgical total mesorectal excision (TME), the optimal time interval between radiation therapy and surgery remains controversial. MATERIALS AND METHODS: Between 1995 and 2005, patients undergoing preoperative radiation therapy and TME for locally advanced mid and low rectal tumors treated in the VU Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment in the VU Medical Center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6-8 weeks in the VU Medical Center (LI group). Preoperative tumor staging, operative data, postoperative complications, pathology results, and follow-up were compared. RESULTS: The SI group (N=57) underwent surgery after a median delay of 4 days and the LI group (N=51) after 45 days. Operative data and short-term morbidity were comparable for both groups. However, significantly higher numbers of complete remissions (12 vs 0%), tumor downstaging (55 vs 26%), and less lymph-node metastases (22 vs 44%) were found in the LI group. No significant differences were found regarding local control or long-term survival after a median follow-up of 34 months. CONCLUSION: Several advantages, such as complete remissions and downstaging in the LI group, do not appear to have expression in a better survival or less local recurrences after a median follow-up of 34 months. Although larger (randomized) studies will be needed for definite conclusions, this may indicate that patients can be operated on within 2 weeks after radiation therapy.