A Comparison Between Radioimmunotherapy and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Carcinomatosis of Colonic Origin in Rats

Background Cytoreductive surgery (CS) followed by heated intraperitoneal chemotherapy (HIPEC) is considered the standard of care for the treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC). These surgical procedures result in a median survival of 2 years at the cost of considerable morbidity and mortality. In preclinical studies, radioimmunotherapy (RIT) improved survival after CS in a model of induced PC of colonic origin. In the present studies we aimed to compare the efficacy and toxicity of CS followed by adjuvant RIT in experimental PC to the standard of care, HIPEC. Methods PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in three groups of Wag/Rij rats. Treatment comprised CS only, CS + RIT or CS + HIPEC, immediately after surgery. RIT consisted of intraperitoneal administration of 74 MBq Lutetium-177 labeled MG1. HIPEC was performed by a closed abdomen perfusion technique using mitomycin C (16 mg/L during 60 minutes). The primary endpoint was survival. Results CS only or combined with RIT was well tolerated. Rats receiving CS + HIPEC were lethargic, suffered from diarrhea, and lost significantly more weight in the first postoperative week. Median survival of rats treated with CS + RIT was significantly longer than after CS alone (97 and 57 days, respectively, P < .004), whereas survival after CS + HIPEC or CS alone were not significantly different (76 and 57 days, respectively, P = .17). Conclusion Survival after CS was significantly improved by RIT with Lutetium-177-MG1 in rats with PC of colorectal origin. Adjuvant HIPEC did not improve survival and was more toxic than adjuvant RIT.     

The Effects of Adjuvant Experimental Radioimmunotherapy and Hyperthermic Intraperitoneal Chemotherapy on Intestinal and Abdominal Healing after Cytoreductive Surgery for Peritoneal Carcinomatosis in the Rat

Background  Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. Methods  PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq ¹⁷⁷lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. Results  At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. Conclusion  As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.     

Intraoperative versus Early Postoperative Intraperitoneal Chemotherapy after Cytoreduction for Colorectal Peritoneal Carcinomatosis: an Experimental Study

Background

Perioperative intraperitoneal chemotherapy is used as an adjunct to cytoreductive surgery (CS) for peritoneal carcinomatosis (PC) in order to prolong survival. Worldwide, hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and combinations of the two are used. It remains unclear which regimen is most beneficial.

Methods

The rat colon carcinoma cell line CC-531 was injected into the peritoneal cavity of 80 WAG/Rij rats to induce PC. Animals were randomized into four treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m² at 41.5°C), CS followed by EPIC during 5 days (i.p. injection of mitomycin on day 1 and 5-fluorouracil on days 2–5), and CS followed by HIPEC plus EPIC. Primary outcome was survival.

Results

In rats treated with CS only, median survival was 53 days (95% confidence interval (CI) 49–57 days). In rats treated with CS followed by HIPEC, survival was significantly (P = 0.001) increased (median survival 94 days, 95% CI 51–137 days). In the group treated with EPIC after CS, 12 out of 20 rats were still alive at the end of the experiment (P < 0.001 as compared with CS only). In the group receiving both treatments, 11 rats died of toxicity, and therefore this group was not included in the survival analysis.

Conclusions

Both EPIC and HIPEC were effective in prolonging survival. The beneficial effect of EPIC on survival seemed to be more pronounced than that of HIPEC. Further research is indicated to evaluate and compare the possible benefits and adverse effects associated with both treatments.

     

Radioimmunotherapy prevents local recurrence of colonic cancer in an experimental model

Background:

Radioimmunotherapy (RIT) is suitable for the treatment of microscopic residual disease and might therefore have an adjuvant role after colonic cancer surgery.

Methods:

An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of 2 × 10⁶ CC531 tumour cells. The biodistribution of ¹¹¹In‐labelled MG1 monoclonal antibody was assessed after intraperitoneal administration. The therapeutic efficacy of ¹⁷⁷Lu‐labelled MG1 (74 MBq per rat), administered on the day of surgery (D0, n = 13) or 5 days later (D5, n = 13), was compared with that of carrier only (n = 13). The primary endpoint was perianastomotic tumour growth 28 days after surgery.

Results:

¹¹¹In‐labelled MG1 preferentially accumulated in perianastomotic CC531 tumours. RIT resulted in a transient reduction in bodyweight in both treatment groups compared with controls, but there were no other signs of clinical discomfort. No macroscopic or microscopic perianastomotic tumour growth was found in eight of 11 animals in the D0 group and 11 of 13 in the D5 group, whereas 11 of 13 controls had macroscopic tumour (P = 0·011 and P = 0·001 respectively).

Conclusion:

This study suggests that RIT may be an effective adjuvant treatment for preventing local recurrence after resection of colonic cancer. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Intraoperative versus Early Postoperative Intraperitoneal Chemotherapy after Cytoreduction for Colorectal Peritoneal Carcinomatosis: an Experimental Study

Background

Perioperative intraperitoneal chemotherapy is used as an adjunct to cytoreductive surgery (CS) for peritoneal carcinomatosis (PC) in order to prolong survival. Worldwide, hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and combinations of the two are used. It remains unclear which regimen is most beneficial.

Methods

The rat colon carcinoma cell line CC-531 was injected into the peritoneal cavity of 80 WAG/Rij rats to induce PC. Animals were randomized into four treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m² at 41.5°C), CS followed by EPIC during 5 days (i.p. injection of mitomycin on day 1 and 5-fluorouracil on days 2–5), and CS followed by HIPEC plus EPIC. Primary outcome was survival.

Results

In rats treated with CS only, median survival was 53 days (95% confidence interval (CI) 49–57 days). In rats treated with CS followed by HIPEC, survival was significantly (P = 0.001) increased (median survival 94 days, 95% CI 51–137 days). In the group treated with EPIC after CS, 12 out of 20 rats were still alive at the end of the experiment (P < 0.001 as compared with CS only). In the group receiving both treatments, 11 rats died of toxicity, and therefore this group was not included in the survival analysis.

Conclusions

Both EPIC and HIPEC were effective in prolonging survival. The beneficial effect of EPIC on survival seemed to be more pronounced than that of HIPEC. Further research is indicated to evaluate and compare the possible benefits and adverse effects associated with both treatments.

     

Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

Background  Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. Methods  Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 × 10⁶ CC531 tumor cells. The biodistribution of ¹¹¹In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of ¹⁷⁷Lu-labeled MG1 was determined and the therapeutic efficacy of ¹⁷⁷Lu-MG1 at MTD was compared with that of ¹⁷⁷Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. Results   ¹¹¹In-MG1 preferentially accumulated in CC531 liver tumors (9.2 ± 3.7%ID/g), whereas ¹¹¹In-UPC-10 did not (0.8 ± 0.1%ID/g). The MTD of ¹⁷⁷Lu-MG1 was 400 MBq/kg body weight. Both the administration of ¹⁷⁷Lu-MG1 and ¹⁷⁷Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received ¹⁷⁷Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of ¹⁷⁷Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of ¹⁷⁷Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). Conclusion  This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors.     

Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies

OBJECTIVE: To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC). SUMMARY BACKGROUND DATA: Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC. METHODS: The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC. RESULTS: The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment. CONCLUSIONS: Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.     

Prognostic factors for peritoneal carcinomatosis originating from colorectal cancer: an analysis of 921 patients from a multi-institutional database

Purpose

The purpose of this study was to clarify the factors affecting R0 resection and the prognosis of patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in the Japanese population.

Methods

A multi-institutional retrospective analysis of 921 patients who underwent surgery between 1991 and 2007 for CRC with PC was conducted. Clinicopathological variables were analyzed for prognostic significance. A multivariate analysis using a Cox regression modeling was performed to assess the prognostic value of the variables.

Results

The median survival time of all patients was 14.3 months (range 0–209 months) and the 5-year overall survival rate was 9.7 %. The multivariate analysis revealed that a lymph node status of pN0/1, the absence of blood-born metastasis, R0 resection and adjuvant chemotherapy favorably affected the survival. Furthermore, the completion of R0 resection was significantly affected by the preoperative serum CEA level, the presence of blood-born metastasis and the grade of PC. The 5-year overall survival and median survival time of the patients with four favorable prognostic factors, namely pN0/1, the absence of blood-born metastasis, R0 resection and adjuvant chemotherapy, were significantly better than those of the remaining patients (37.1 vs. 7.2 % and 37.0 vs. 13.3 months, respectively; p < 0.0001).

Conclusions

Although few patients with PC from CRC survive for more than 5 years, performing R0 resection with curative intent in association with postoperative adjuvant chemotherapy should be considered in appropriately selected patients.     

Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation

Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single‐center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney‐alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient (P < 0.0001), longer CS time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post‐transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation.     

Prognostic Factors and Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Background  The aim of this study was to determine prognostic factors for survival after resection of pancreatic adenocarcinoma (PC) and to compare outcomes after surgery alone versus surgery plus adjuvant therapy. Methods  We performed a retrospective review of 219 patients who underwent pancreaticoduodenectomy for PC with curative intent between 1995 and 2007. Data were collected prospectively. Postoperative adjuvant chemoradiation therapy (CRT) consisted of fluorouracil or gemcitabine-based chemotherapy; the median radiation dose was 45 Gy. Results  The 3- and 5-year overall survival (OS) rates were 24.3% and 14.2%, respectively. Median OS was 14.0 months [95% confidence interval (CI), 12–16 months]. Patients with metastatic lymph nodes experienced improved median survival (16 vs 10 months; P < 0.001) and 3-year OS (3-year OS 28% vs 8%) after adjuvant CRT compared with those who had no CRT. Patients who underwent non-curative resection had the same effect (median OS, 13 vs 8 months; P = 0.037). Lymph node metastasis and non-curative resection showed no significance on multivariate analysis. Poor differentiation [risk ratio (RR) = 2.10; P < 0.001] and tumor size >3 cm (RR = 1.57; P = 0.018) were found to be adverse prognostic factors; adjuvant CRT had borderline significance (RR = 0.70; P = 0.087). Conclusions  Adjuvant CRT benefited a subset of patients with resected PC, particularly those with lymph node metastasis and those undergoing non-curative resection. Multivariate analysis demonstrated that patients with tumors larger than 3 cm and poor differentiation had poor prognosis.     

Preoperative neutrophil to lymphocyte ratio >5 is a prognostic factor for recurrent colorectal cancer

Aim Previous studies have demonstrated that raised preoperative neutrophil to lymphocyte ratio (NLR) is associated with poor prognosis in colorectal cancer (CRC). The aim of this study was to assess whether preoperative NLR could predict patients at risk of recurrence of CRC. Method All consecutive patients who underwent surgical resection for CRC over a 2‐year period at our institution were analysed. Demographic data including CRC recurrence were prospectively collected from our institutional cancer database. CRC recurrence was diagnosed on radiological and endoscopic histopathological data. Preoperative NLR was calculated on baseline blood results, with a value >5 being a poor prognostic factor. Parametric survival analysis was used to identify risk factors for CRC recurrence. Hazard ratios (HRs) were calculated for gender, CRC stage using Jass score, preoperative NLR and CRC site. P < 0.05 was considered statistically significant. Results In all, 297 patients (157 men) underwent CRC resection at a median age of 70 years (range 23–93); 164 patients had colon cancer, 111 rectal cancer and 22 recto‐sigmoid cancer. The distribution by stage of CRC was 30.2% for stage 1, 23.8% for stage 2, 19.5% for stage 3 and 26.5% for stage 4. Over a median follow‐up period of 3.35 (0.1–8) years, 59 (19.8%) patients had recurrent CRC. Multivariate analysis revealed CRC stage (HR 8.69, 95% CI 3.85–19.6, P < 0.0001) and NLR >5 (HR 1.81, 95% CI 1.07–3.07, P = 0.028) to be significant and independent risk factors predictive of recurrent CRC. Conclusion These data suggest that preoperative NLR >5 is predictive of CRC recurrence.     

The 2-week wait referral system does not improve 5-year colorectal cancer survival

Aim The aim of this study was to compare 5‐year survival rates in colorectal cancer (CRC) patients who underwent potentially curative surgery before and after the introduction of the 2‐week wait (2WW) referral system. Method Data were collected retrospectively from a prospectively maintained cancer database for CRC patients who underwent surgery in 1999 (pre‐2WW group, n = 150) and 2002 (post‐2WW group, n = 126). Patients who presented as an emergency, those who died within 30 days of surgery and those who presented with incurable CRC were excluded. We used the Kaplan–Meier method to plot survival curves and the log rank test to compare survival rates between the two groups. Results The 5‐year survival rates in the pre‐2WW and post‐2WW groups did not differ significantly (71%vs 72%, respectively; P = 0.880). The number of CRC patients who presented via urgent pathways was higher in the post‐2WW group than in the pre‐2WW group (77%vs 38%, P < 0.001). Further, owing to this change in the referral pattern, the overall delay between referral and treatment was significantly lower in the post‐2WW group than in the pre‐2WW group (median 76 days vs 115, P = 0.009). Conclusion The 2WW referral system for patients with symptoms of CRC does not translate into improved survival. However, more patients with symptomatic CRC are being referred via urgent pathways.     

Impact of Aggressive Histology and Location of Primary Tumor on the Efficacy of Surgical Therapy for Peritoneal Carcinomatosis of Colorectal Origin

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) of colorectal origin increases survival (OS) compared to systemic chemotherapy alone. Signet ring histology demonstrates aggressive behavior with poor survival. We sought to determine whether CRS/HIPEC increases survival in this subset of patients.

Methods

We reviewed 67 patients with PC of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology from a prospective database between May 2001 and August 2011. Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival.

Results

Complete CRS (CC-0/1) was achieved in 77 % (CRC) and 73 % (AP) of patients. Progression-free survival (PFS) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients. In the CRC group, univariate predictors of poor survival included female gender, age, American Society of Anesthesiologists score, preoperative albumin, completeness of cytoreduction, and morbidity. In a multivariate Cox regression model, incomplete cytoreduction (CC-2/3) and female gender were joint significant predictors of poor survival. In the AP group, significant univariate predictors of poor survival included higher EBL and PCI score. In a multivariate Cox regression model, blood loss of >500 ml and a body mass index of <25 kg/m² were joint significant predictors of poor survival.

Conclusions

AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis, suggesting an underlying difference in biology. CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved, whereas appendiceal signet ring carcinomatosis may benefit, regardless of resectability.     

The impact of lymph node yield on Duke’s B and C colorectal cancer survival

Aim The number of positive lymph nodes retrieved following colorectal cancer (CRC) resection impacts on the staging and further treatment of the disease. We compared 5‐year survival by lymph node yield for Duke’s B and C patients to assess the impact on prognosis. Method A retrospective methodology was employed to review patients who underwent operative resection for Duke’s B or C CRC between 1999 and 2003. Results A total of 351 patients were included in our analyses. Lymph node yield, N‐stage and extramural vascular invasion were independent predictors of overall 5‐year survival. A significant difference in 5‐year survival by lymph node yield was seen among Duke’s B patients (< 9 nodes vs≥ 9 nodes, 45.2%vs 68.4%; P = 0.0043) and Duke’s C patients (< 10 nodes vs≥ 10 nodes, 25.6%vs 48.8%; P = 0.0099). There was a significant reduction in the relative risk of 2.8% in mortality for each additional node sampled in Duke’s B and C patients (RR 0.972, 95% confidence interval 0.949–0.994, P = 0.0102). Duke’s B patients who had < 9 lymph node yield and no neoadjuvant/adjuvant treatment had a similar survival to all Duke’s C patients (47.8%vs 41.7%, P = 0.5136). Conclusion Lymph node yield independently predicts for survival in patients with Duke’s B and C CRC. Duke’s B patients with < 9 lymph node yield have no better survival than patients with Duke’s C disease. Therefore, prospective randomized studies are required to examine if inadequate lymph node yield could be one of the deciding factors in offering adjuvant therapy among Duke’s B cancer patients.     

Metabolic Syndrome after Laparoscopic Bariatric Surgery

Background  Metabolic syndrome (MS) is common among morbidly obese patients undergoing bariatric surgery. The aim of this study was to assess the impact and predictors of bariatric surgery on the resolution of MS. Methods  Subjects included 286 patients [age 44.0 ± 11.5, female 78.2%, BMI 48.7 ± 9.4, waist circumference 139 ± 20 cm, AST 23.5 ± 14.9, ALT 30.0 ± 20.1, type 2 diabetes mellitus (DM) 30.1% and MS 39.2%] who underwent bariatric surgery. Results  Of the entire cohort, 27.3% underwent malabsorptive surgery, 55.9% underwent restrictive surgery, and 16.8% had combination restrictive–malabsorptive surgery. Mean weight loss was 33.7 ± 20.1 kg after restrictive surgery (follow up period 298 ± 271 days), 39.4 ± 22.9 kg after malabsorptive surgery (follow-up period 306 ± 290 days), and 28.3 ± 14.1 kg after combination surgery (follow-up period 281 ± 239 days). Regardless of the type of bariatric surgery, significant improvements were noted in MS (p values from <0.0001–0.01) as well as its components such as DM (p values from <0.0001–0.0005), waist circumference (p values <0.0001), BMI (p values <0.0001), fasting serum triglycerides (p values <0.0001 to 0.001), and fasting serum glucose (p values <0.0001). Additionally, a significant improvement in AST/ALT ratio (p value = 0.0002) was noted in those undergoing restrictive surgery. Multivariate analysis showed that patients who underwent malabsorptive bariatric procedures experienced a significantly greater percent excess weight loss than patients who underwent restrictive procedures (p value = 0.0451). Percent excess weight loss increased with longer postoperative follow-up (p value <0.0001). Conclusions  Weight loss after bariatric surgery is associated with a significant improvement in MS and other metabolic factors.     

Results of Treatment of 385 Patients With Peritoneal Surface Spread of Appendiceal Malignancy

Introduction: In the past, peritoneal carcinomatosis, regardless of primary tumor type, has always been a lethal condition. Recently, special treatments using cytoreductive surgery with peritonectomy procedures combined with perioperative intraperitoneal chemotherapy have resulted in long-term survival. Appendiceal malignancy with a low incidence of liver and lymph node metastases may be especially appropriate for these aggressive local regional treatments.Methods: All patients treated with surgery before January 1999 are included. Patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy. The intraperitoneal chemotherapy was given in the perioperative period, starting with mitomycin C at 12.5 mg/m² for males and 10 mg/m² for females. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theater with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, five consecutive days of intraperitoneal 5-fluorouracil at 650 mg/m2 instilled in 1–1.5 liters of 1.5% dextrose peritoneal dialysis solution. A complete cytoreduction was defined as tumor nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as having adenomucinosis, adenomucinosis/carcinomatosis hybrid, or mucinous carcinomatosis. A previous surgical score was used to estimate the extent of previous surgical procedures.Results: The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P < .0001), the histopathological character of the appendix malignancy (P < .0001), and the extent of previous surgical interventions (P = .001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; with hybrid pathology, survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years.Conclusions: Cytoreductive surgery and perioperative intraperitoneal chemotherapy can be used to salvage selected patients with peritoneal surface spread of appendiceal primary tumors. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999     

Undertreatment of Gallbladder Cancer: A Nationwide Analysis

Background

Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer.

Methods

Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004–2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan–Meier and Cox proportional hazard methods.

Results

The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p?<?0.0001), private insurance (41.6% vs 27.1%; p?<?0.0001), academic centers (50.4% vs 29.7%; p?<?0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p?=?0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p?=?0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p?<?0.0001), negative margins on final pathology (90.1% vs 72.6%; p?<?0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p?<?0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p?<?0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p?=?0.0004).

Conclusions

Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.

     

Reduced Lymph Node Yield in Rectal Carcinoma Specimen After Neoadjuvant Radiochemotherapy Has No Prognostic Relevance

Background  In colorectal surgery UICC/AJCC criteria require a yield of 12 or more locoregional lymph nodes for adequate staging. Neoadjuvant radiochemotherapy for rectal carcinoma reduces the number of lymph nodes in the resection specimen; the prognostic impact of this reduced lymph node yield has not been determined. Methods  One hundred two patients with uT3 rectal carcinoma who were receiving neoadjuvant radiochemotherapy were compared with 114 patients with uT3 rectal carcinoma who were receiving primary surgery followed by adjuvant radiochemotherapy. Total lymph node yield and number of tumor-positive lymph nodes were determined and correlated with survival. Results  After neoadjuvant radiochemotherapy both total lymph node yield (12.9 vs. 21.4, p < 0.0001) and number of tumor-positive lymph nodes (1.0 vs. 2.3, p = 0.014) were significantly lower than after primary surgery plus adjuvant radiochemotherapy. Reduced total lymph node yield in neoadjuvantly treated patients had no prognostic impact, with overall survival of patients with 12 or more lymph nodes the same as that of patients with less than 12 lymph nodes. Overall survival of neoadjuvantly treated patients was significantly influenced by the number of tumor-positive lymph nodes with 5-year-survival rates of 88, 63, and 39% for 0, 1–3, and more than 3 positive lymph nodes (p < 0.0001). Conclusion  The UICC/AJCC criterion of a total lymph node yield of 12 or more should be revised for rectal carcinoma patients. D. Doll and R. Gertler contributed equally to this work.     

The Effect of Treatment for Colorectal Cancer on Long-Term Health-Related Quality of Life

Background: Little information is available on the impact that therapies used in the treatment of colorectal cancer (CRC) have on long-term, health-related quality of life (HRQL). Knowledge of how HRQL is affected by these therapies is essential in properly selecting patients for treatment. The purpose of this study was to determine the long-term impact that surgical and adjuvant therapy for resectable CRC has on patient-reported HRQL in a male veteran population through a case-control design.Methods: All participating patients had completed therapy at least 6 months before enrollment. One hundred fifty-eight patients were accrued over a 3-year period (January 1, 1997 to December 31, 1999) at a single institution. The impact of CRC surgery on HRQL was measured by comparing a cohort of 61 patients undergoing surgery alone for the treatment of CRC (CRC-S group) with 44 patients undergoing surgery for benign colonic disease (BCD group). To study the effect of adjuvant therapy for CRC on HRQL, a third cohort of 53 patients undergoing both surgical and adjuvant treatment (CRC-S/A group) was compared with the CRC-S group. For each group, health status was measured by a health survey questionnaire, SHORT FORM 36 (SF36). For patients treated for CRC, an additional disease-specific supplemental questionnaire also was used.Results: Self-reported health status, as measured by mean SF36 score, was significantly reduced for the BCD group compared with CRC-S patients on general health perception (41.9 ± 3.9 vs. 52.2 ± 3.0, P = .04) and the standardized physical component score (31.2 ± 1.7 vs. 37.5 ± 1.5, P < .005). Despite an increased number of distally located tumors, later stage cancers, and an increased number of recurrences in the CRC-S/A group compared with the CRC-S cohort, no significant differences were identified between these groups on any of the subscales or standardized scores of SF36. Using the supplemental questions, no differences were identified between the CRC groups with respect to appetite, weight, or gastrointestinal or urinary functioning.Conclusions: Surgical therapy for CRC probably has minimal impact on long-term HRQL when compared with surgery for benign colonic processes. Similarly, there does not appear to be a measurable, lasting impact of CRC adjuvant therapy on HRQL when compared with surgery alone. Although overall impact of therapies for CRC on HRQL appears to be limited, measurement of therapeutic influence on an individual level and identification of selection criteria based on estimated impact on HRQL for these therapies requires prospective validation.     

Independent Risk Factors for Ventilator-Associated Pneumonia After Cardiac Surgery

ABSTRACT

Objective: To investigate the related factors and pathogens of ventilator-associated pneumonia (VAP) after heart surgery so as to provide evidences for clinical prevention and therapy. Methods: In total 1,688 cases were collected from January 2004 to January 2011. Overall 105 patients developed VAP. Retrospectively analyzed these patients after heart surgery to determine the clinical data, pathogens and treatment measures. Results: The frequency of ventilator-associated pneumonia was 6.2% (105/1 688), and mortality was 25.7% (27/105), 198 pathogen strains were isolated by bacterial culture, in which Gram negative bacteria accounted for 69.2% (137/198), Gram positive bacteria 27.8% (55/198), and fungi 3.0% (6/198). The independent risk factors for VAP after cardiac surgery were: age >70 (p < .01), emergent surgery (p < .01), perioperative blood transfusions (p < 0.01), reintubation (p < .01) and days of mechanical ventilation (MV) (p < .01). Median length of stay in the ICU for patients who developed VAP or not was, respectively, (24.7 ± 4.5) days versus (3.2 ± 1.5) days (p < .05), and mortality was, respectively, 25.7% versus 2.9% in both populations (p < .05). Conclusion: Age >70, emergent surgery, perioperative blood transfusions, reintubation and days of MV are the risk factors for VAP in patients following cardiac surgery. P. aeruginosa, P. klebsiella, S. aureus, and Acinetobacter baumannii were the main pathogens of VAP. According to the cause of VAP, active prevention and treatment measures should be developed and applied to shorten the time of MV and improve chances of survival.