Preoperative Nutritional Status Predicts Major Morbidity After Primary Rectal Cancer Resection.

BACKGROUND: Malnutrition has been associated with adverse surgical outcomes, but data regarding its impact specifically in rectal cancer are sparse. The goal of this study was to use national data to determine the effects of malnutrition on surgical outcomes in rectal cancer resection. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from the years 2012-2015. Patients were included on the basis of International Classification of Disease 9/10 and Current Procedural Terminology codes for rectal cancer and proctectomy. Malnutrition was defined as body mass index <18.5 kg/m2, weight loss >10% in 6 mo, or preoperative albumin <3.5 mg/dL. Associations between malnutrition and postoperative outcomes were assessed by the Student t-test and chi-square test. Multivariate regression models were constructed to adjust for potential confounders of the association between malnutrition and surgical outcomes. RESULTS: Of the 9289 patients with primary rectal cancer who underwent resection, 1425 (15%) were in a state of malnutrition at the time of surgery. Patients with malnutrition had longer mean length of stay (LOS), and higher rates of 30-d mortality, wound infection, organ-space infection, sepsis, reoperation, prolonged LOS (>30 d), failure to wean off ventilator, renal failure, and cardiac arrest. With the exception of LOS, renal failure, and organ-space infection, malnutrition was still significantly associated with higher rates of these adverse outcomes after adjustment for confounders in multivariate regression models. CONCLUSIONS: Malnutrition is a practical marker associated with a variety of adverse outcomes after rectal cancer surgery, and it represents a potential target for nutritional therapies to improve surgical outcomes.

Morbidly Obese Patients with Ileocolic Crohn's Disease May Benefit from Robotic Surgery.

BACKGROUND AND OBJECTIVES: Obesity is increasing as a comorbid condition for patients requiring surgery for Crohn's disease. Minimally invasive colectomy is ideal for a patient with combined obesity and Crohn's disease. However laparoscopic colon resection is associated with high operative conversion rates in these cases. Data examining the use of robotic surgery in the obese patient with Crohn's disease is sparse. METHODS: We examined the feasibility and outcomes of performing a minimally invasive colectomy using the Da Vinci robot in a prospective case series of morbidly obese patients with ileal Crohn's disease. RESULTS: A robotic ileocolectomy was performed in four morbidly obese patients with Crohn's disease. There were no operative conversions or complications with a median length of stay of 3 days. CONCLUSION: A robotic approach is a promising minimally invasive surgical alternative to laparoscopic surgery for these complex patients.

Robotic colectomy with intracorporeal anastomosis is feasible with no operative conversions during the learning curve for an experienced laparoscopic surgeon developing a robotics program.

The benefits of performing a colectomy robotically instead of laparoscopically have not conclusively been demonstrated. Evaluation of studies is limited by sample size, retrospective design, heterogeneity of operative techniques, sparse adjustment for learning curve, and mixed results. Consequently, adoption of robotic colectomy by surgeons has been expectedly slow. The objectives of the study were to compare the outcomes of robotic colectomy to laparoscopic colectomy for patients with right-sided tumors undergoing a standardized completely intracorporeal operation and to examine the impact of prior experience with laparoscopic right colectomies on the performance of robotic right colectomies. Retrospective review of outcomes of consecutive patients undergoing a robotic right colectomy (robot) compared to those undergoing laparoscopic colectomy (LAP). LAP patients were further subdivided into a group during the learning curve (LC) and after the learning curve (post-LC). Data collected included operative time (OT), conversion to laparotomy, lymph nodes harvested (LN), length of stay (LOS), 30-day morbidity, and mortality. Comparison of continuous and categorical variables was assessed with the independent samples t test and Chi-square test, respectively. Data are expressed as mean ± SD, and significance defined as p < 0.05. 122 patients underwent robot (n = 21), LAP (n = 101), LC (n = 51), or post-LC (n = 50). OT was decreased for post-LC compared to LC (198 vs. 228 min). There were no conversions in robot and five with LAP. Morbidity was similar for robot (14%) compared to LAP (22%), LC (24%), or post-LC cases (20%). Median LOS was similar for robot vs. LAP (3 vs. 5 days). Robot had greater mean LN yield vs. LAP (19 vs. 14, p = 0.02). The initial outcomes with completely intracorporeal colectomy achieved robotically were equivalent to results during or after LC for laparoscopic resection. Proficiency gained with LAP seems to positively impact the initial results with the robot.

Operative Mortality Prediction for Primary Rectal Cancer: Age Matters.

BACKGROUND: The risk of colorectal cancer increases with age, and the number of older adults requiring operations has increased. The purpose of this study was to determine whether a current risk calculator can accurately predict operative mortality for rectal cancer and whether the predictive accuracy varied with age. METHODS: The American College of Surgeons NSQIP database using ICD-9/10 codes for rectal cancer and CPT codes for proctectomy was accessed (2012 to 2015). The prognostic value of the risk calculator was evaluated using the predicted mortality variable code. Age categories were 18 to 64 years, 65 to 79 years, and 80 to 89 years. Analysis of variance was performed to assess differences between age categories in predicted and actual mortality and Pearson correlation coefficients were computed. Logistic regression models were constructed to evaluate associations adjusted for key covariates. RESULTS: There were 9,289 patients included, with age distribution as follows: 18 to 64 years (n = 5,674), 65 to 79 years (n = 2,899), and 80 to 89 years (n = 716). Both predicted and actual mortality increased with age, adjusting for functional status, comorbidity, and other covariates (p < 0.0001). The overall correlation between predicted and actual mortality was low (r = 0.20). The correlation was weakest from 18 to 64 years (r = 0.07), strongest from 65 to 79 years (r = 0.25), and in between from 80 to 89 years (r = 0.13). Predicted mortality was overestimated in the 18 to 64 years and underestimated in both the 65 to 79 years and 80 to 89 years age groups. Predicted mortality by age category interaction terms was also significantly associated with actual mortality in covariate-adjusted logistic regression models, providing additional evidence that the accuracy of predicted mortality varies by age. CONCLUSIONS: The American College of Surgeons NSQIP mortality risk estimates appear to be poorly associated with actual mortality and the accuracy might differ between younger and older patients with primary rectal cancer. Goals of care discussion with the older patient about outcomes are indicated, as there is an almost twice predicted mortality.

Should completely intracorporeal anastomosis be considered in obese patients who undergo laparoscopic colectomy for benign or malignant disease of the colon?

BACKGROUND: The outcome of laparoscopic colectomy with completely intracorporeal anastomosis (LCIA) in obese and nonobese patients is assessed. METHODS: Forty-five consecutive patients who underwent LCIA for benign or malignant disease of the right and proximal left colon were reviewed prospectively. Obesity was defined as a body mass index of >30 kg/m(2). RESULTS: There were 24 men (53%) and 21 women (47%) with a mean age of 67 years (46-84 years). The mean body mass index was 27 kg/m(2) (16-38 kg/m(2)); 13 patients (29%) were obese. One procedure was converted to a laparoscopic-assisted colectomy. The mean operative time, estimated blood loss, and duration of stay were 218 minutes (110-420 minutes), 82 mL (50-250 mL), and 5 days (2-11 days), respectively. The mean length of the larger incision (extraction site) and the sum of all port incisions was 4 cm (3-8 cm) and 7 cm (6-10 cm), respectively. Complications occurred in 8 of 45 patients (18%), with no deaths. The mean number of harvested lymph nodes per specimen was 11 (3-30 lymph nodes). Obesity had no effect on operative time (obese patients, 232 minutes; nonobese patients, 213 minutes), incision length (obese patients, 4 cm; nonobese patients, 4 cm) estimated blood loss (obese patients, 100 mL; nonobese patients, 76 mL), complications (obese patients, 15%; nonobese patients, 19%), duration of stay (obese patients, 5 days; nonobese patients, 5 days), or number of harvested lymph nodes (obese patients, 11 lymph nodes; nonobese patients, 11 lymph nodes). There were no port-site hernias or metastases during a mean follow-up period of 5 months (1-18 months). CONCLUSIONS: LCIA can offer smaller incisions, improved cosmesis, and low conversion rates while oncologic principles are preserved. LCIA is a feasible and safe technique with equally successful outcomes in thin and obese patients.

Microdissection-based allelotyping: a novel technique to determine the temporal sequence and biological aggressiveness of colorectal cancer.

Pathologic staging in colorectal adenocarcinoma (CA) is based on the concept that the timing of metastatic tumor spread is directly related to the depth of the primary tumor invasion. To evaluate the temporal sequence of CA metastasis, we performed microdissection mutational profiling at multiple microscopic sites of primary and metastatic CA specimens. Twenty-one cases of CA were selected from fixed-tissue archives. Primary tumors were microdissected at the deepest point of invasion. Comparative mutational profiling for different genomic loci [1p36(CCM = cutaneous malignant melanoma], 3p26(OGGI = 8 oxoguanine DNA glycosylase), 5q23 (APC, MCC = mutated in colorectal cancer), 9p21(p16/CDKN2A = cyclin-dependent kinase 2A), 10q23(PTEN = phosphatase and tensin homolog [mutated in multiple advanced cancers 11), 12p12(K-ras-2 point mutation), 17p13(TP53), 18q25(DCC= deleted in colorectal cancer) was carried out on each microdissected tissue target using microsatellite loss of heterozygosity determination or DNA sequencing. All primary and metastatic sites of CA manifested acquired mutational change in 18 to 91 per cent of the genomic markers. In 15/21 (71%) cases, metastatic sites lacked a specific allelic loss seen in the corresponding primary tumor, indicating that the metastasis occurred before maximal depth of primary invasion. This was further supported by discordant mutational profiles between primary and secondary tumors, requiring divergent clonal evolution. This is the first report describing the temporal sequence and significance of sequential mutational acquisition in clinical tissue specimens with potential implications for a new molecular pathology approach to classify human cancer.

Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53.

Nitric oxide (NO) is a potent tumor radiosensitizer; however, its clinical use is limited by systemic side effects. We have demonstrated previously that gene transfer of the human inducible NO synthase (iNOS) gene into tumor cells and tumors induces high-output NO production that significantly enhances tumor radioresponsiveness, with no observed side effects. Notably, iNOS gene transfer enhances tumor radioresponsiveness via apoptotic cell death. Because NO and ionizing radiation are both known to promote p53-dependent apoptosis, we hypothesized that p53 activation might be a primary mechanism for the synergy of these two genotoxic stresses. We report that NO and ionizing radiation synergistically activate p53 in colorectal cancers grown in athymic mice by augmenting phosphorylation of p53 at serine 15. The effect of NO and ionizing radiation on tumor cell apoptosis and tumor radioresponsiveness is significantly reduced in p53 knockout isogenic cancer cell lines. Furthermore, the transfer of both p53 and iNOS genes into tumor cells lacking functional p53 enhanced their radioresponsiveness more than transfer of either gene alone.

Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity.

Nitric oxide is a potent radiosensitizer of tumors, but its use clinically is limited by serious side effects when administered systemically. We have demonstrated previously that gene transfer of the inducible nitric oxide synthase gene (iNOS) into colorectal cancer cells enhances radiation-induced apoptosis in vitro. The objectives of this study were to further characterize the effects of iNOS gene transfer on the radiosensitivity of human colorectal cancer cells in vitro and tumors grown in athymic nude mice. Adenoviral gene transfer of iNOS (AdiNOS) into human colorectal cancer cell lines (HCT-116 and SNU-1040 cells) significantly enhanced the effects of radiation with sensitizing enhancement ratios (0.1) of 1.65 and 1.6, respectively. The radiation enhancement induced by iNOS was associated with increased iNOS expression and nitric oxide production and prevented by L-NIO, an enzymatic inhibitor of iNOS. AdiNOS treatment of HCT-116 tumors combined with radiation (2 Gy x three fractions) led to a 3.4-fold greater (P < 0.005) tumor growth delay compared with radiation (RT) alone. AdiNOS plus RT also caused significant (P < 0.01) tumor regression with 63% of tumors regressing compared with only 6% of tumors treated with RT. AdiNOS plus RT significantly (P < or = 0.001) increased the percentage of apoptotic cells (22 +/- 4%) compared with either tumors treated with control vector plus RT (9 +/- 1%), AdiNOS alone (9 +/- 3%), or no treatment (2 +/- 1%). These radiosensitizing effects of AdiNOS occurred at low infection efficiency (4% of tumor infected), indicating a significant bystander effect.

Short-term results of treating primary and recurrent anal fistulas with a novel extracellular matrix derived from porcine urinary bladder.

Anal fistulas are difficult to treat because they are often recalcitrant to medical therapies and surgical treatment may lead to significant morbidities. A recent novel biologically derived graft from porcine urinary bladder (MatriStem(TM)) has shown great promise in experimental studies of tissue regeneration in diverse tissues. The objectives of this study were to evaluate the safety and short-term efficacy of MatriStem for treatment of anal fistulas. This was a retrospective study of patients treated from January 3, 2012 to March 3, 2014 at the University of Pittsburgh Medical Center. MatriStem was used to treat patients with anal fistulas by implanting it uniformly with a single application in all patients using a standardized protocol. Data were collected retrospectively from hospital records and office charts. Nineteen fistulas were treated with MatriStem. There were no adverse complications. Overall efficacy of MatriStem was 79 per cent with healing occurring in a mean time of 17 days and mean follow-up of seven months (range 1-26 months). MatriStem was effective in healing in 75 per cent of primary anal fistulas and 86 per cent of recurrent fistulas. MatriStem seems to be a safe and promising treatment for primary and recurrent anal fistulas, and warrants further study and clinical trials to substantiate widespread clinical use.

Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury.

Small bowel toxicity represents a major dose-limiting side effect of radiation treatment for many malignancies. We examined the effects of overexpressing human manganese superoxide dismutase (MnSOD) in the small intestine in mice to prevent radiation enteritis. Mice were treated with the human MnSOD gene delivered enterally using a nontoxic, replication-defective herpes simplex virus (HSV)-1-based vector. HSV vectors containing the human MnSOD transgene and green fluorescent protein (GFP) transgene, or GFP transgene alone, were constructed and injected intraluminally into a 2cm length of small intestine of C3H/HeNsd mice. Total body irradiation of 15 Gy was delivered to mice inoculated 24 hours earlier with either HSV-MnSOD (10(3) to 10(8) plaque-forming units), control HSV-GFP, or no vector. At 24 or 72 hours after irradiation, mice were killed and villi areas were measured from appropriate segments of the small intestine. Control irradiated mice showed a decreased villi area of 82% by day 3 after irradiation, whereas treatment of mice with HSV-MnSOD 10(8) plaque-forming units led to only a 16% decrease in villi area (P < 0.001) before radiation. Similar findings were seen on day 3 and were associated with a significant (P < 0.001) preservation of enteric protein content in HSV-MnSOD-treated mice. A dose-dependent effect of MnSOD in preventing radiation-induced small bowel injury was evident. These data demonstrate that overexpression of human MnSOD via a replication-defective herpes viral vector is an efficacious method of protecting the small intestine from ionizing radiation damage.

Laparoscopic colectomy is feasible in the mega-obese patient using a standardized technique.

The use of laparoscopic colectomy in morbidly obese individuals is controversial. There are significant safety issues including increased risk of bleeding, increased anastomotic leak and high operative conversion rates. We report the first successful laparoscopic colectomy in a patient with the most extreme category of morbid obesity, mega-obesity (body mass index [BMI]>70). We describe a standardized technique using a completely intracorporeal technique with all resection lines reinforced with a bioabsorbable staple line reinforcement material. This technique has the potential of making laparoscopic colectomy more feasible for patients with morbid obesity in general.

A case-control study examining the benefits of laparoscopic colectomy using a totally intracorporeal technique for left-sided colon tumors.

Laparoscopic-assisted colectomy with an extracorporeal anastomosis is associated with a higher conversion rate for left-sided colon tumors. We hypothesized that a totally intracorporeal laparoscopic colectomy (TILC) would minimize operative conversion and morbidity. We conducted a case-control study comparing TILC for left-sided and right-sided tumors with matching based on age and ASA status. TILC was performed for 105 colon tumors with an overall conversion rate of 6.5%, a complication rate of 22%, and median length of stay of 5 days. There were 35 patients undergoing TILC for left-sided colon tumors and 70 patients undergoing TILC for right-sided colon tumors. Operative conversion for left-sided TILC (6%) was similar (P=0.78) to right-sided TILC (7%). Complication rates for left-sided TILC (23%) were no different (P=0.87) compared with right-sided TILC (21%). Length of stay for left-sided TILC (5 d) was comparable (P=0.17) to right-sided TILC (5 d). Laparoscopic left colectomy can be successfully performed with equivalent results to laparoscopic right colectomy by using a totally intracorporeal technique.

Totally intracorporeal laparoscopic colectomy (TILC) is associated with similar surgical outcomes in high and low operative risk patients.

PURPOSE: Patients undergoing laparoscopic-assisted colectomy with obesity, high American Society of Anesthesiologists (ASA) grade, and left-sided colon tumors are at high risk for operative conversion and complications. We hypothesized that a completely intracorporeal laparoscopic colectomy would be beneficial for high-risk patients compared with healthy, low-risk patients. METHODS: We conducted a retrospective study of 136 consecutive patients undergoing a standardized totally intracorporeal laparoscopic colectomy for neoplasms from February 2004 to September 2011. Patients were stratified into a high-risk group with 1 or more factors: body mass index >30, ASA grade ≥ 3, and left-sided tumors or a low-risk group with no factors. Variables compared were case frequency during the learning curve, body mass index, estimated blood loss, operative time, conversion, 30-day complications, and length of stay. Comparisons between groups were made by χ2 analysis or t test where appropriate. Data are expressed as median ± SD, odds ratio, and significance defined as P<0.05. RESULTS: Laparoscopic colectomy was performed in 136 patients with a conversion rate of 4%. There were 86 high-risk patients and 50 low-risk patients. High-risk patients had a significantly (P<0.005) longer operative time (225 ± 66 vs. 186 ± 55 min) but no significant difference in estimated blood loss, conversion rates, learning curve, complications, or length of stay compared with low-risk patients. CONCLUSIONS: When laparoscopic colectomy is performed totally intracorporeally, surgical outcomes in high-risk patients with obesity, high ASA grade, and left-sided tumors are equally successful to results achieved for low-risk patients that are thin, healthy, with right-sided lesions.

Laparoscopic colon resection of benign polyps: high grade dysplasia on endoscopic biopsy and polyp location predict risk of cancer.

BACKGROUND: To ensure that an oncologic resection is not compromised, laparoscopic surgery is not recommended for colon cancer patients during the learning curve. Although patients with colon polyps are frequently selected as "learning cases," several studies have found a high incidence of occult cancers in this subset of patients questioning the safety of this approach. A retrospective review was performed of laparoscopic resections for colonic polyps to determine the incidence of occult cancer and, clinical and pathologic factors predictive of cancer. METHODS AND RESULTS: From January 2004 and September 2007, 44 colectomies were performed for colonic polyps. Data from a prospective database was examined and supplemented by pathology reports. Of 44 patients, operative conversion was 5% with a 4-day median length of stay, a morbidity of 20% with no mortalities. All patients had clear surgical margins with a median of 12 lymph nodes detected. An occult cancer was detected in 6 of 44 cases (14%). High-grade dysplasia on endoscopic biopsy and polyp location distal to the splenic flexure was associated with a significantly (P<0.05) increased risk of cancer. Forty-three percent of cancers were detected in polyps with high-grade dysplasia compared with 8% of polyps without dysplasia on biopsy. Polyps distal to the splenic flexure had a 43% rate of occult cancers detected compared with 8% in polyps proximal to the splenic flexure. CONCLUSIONS: Colonic polyps with high-grade dysplasia on endoscopic biopsy and polyps located distal to the splenic flexure are associated with the highest risk of cancer and may not be appropriate cases during the learning curve.

Laparoscopic colectomy performed using a completely intracorporeal technique is associated with similar outcome in obese and thin patients.

BACKGROUND: Despite the potential benefits of laparoscopic-assisted colectomy, it is often associated with high operative conversion rates and increased morbidity especially in patients with obesity. OBJECTIVES: The goal of this study was to evaluate the results of a completely intracorporeal laparoscopic approach in patients including those with obesity. METHODS: Laparoscopic colectomy was attempted in 85 patients between November 2003 and April 2007. Patients were prospectively followed to determine operative time (OT), blood loss, operative conversion, length of stay, 30 days morbidity, and lymph nodes harvested. RESULTS: Operative conversion was 2%, mean estimated blood loss was 95+/-84 mL, and mean OT was 220+/-64 minutes. There were no anastomotic leaks or perioperative mortalities. There were 9 major complications (11%). Obese patients (n=25) compared with thin patients (n=58) had similar operative conversion (4% vs. 2%), OT (220+/-73 min vs. 220+65 min), lymph nodes harvested (13+/-6 vs. 11+/-6), major complication rates (16% vs. 9%), and length of stay (5.0+/-2.7 d vs. 4.9+/-1.7 d). CONCLUSIONS: Laparoscopic colectomy using a completely intracorporeal technique leads to similar surgical results in obese and thin patients.

Is operative conversion necessary for patients diagnosed with dense adhesions during an elective laparoscopic colectomy?

UNLABELLED: Laparoscopic colectomy is often complicated by adhesions. Studies examining the morbidity of laparoscopic lysis of adhesions (LOA) combined with colectomy are sparse. OBJECTIVES: The goal of this study was to prospectively evaluate the results of using the harmonic scalpel to lyse adhesions in patients undergoing laparoscopic colectomy. METHODS: Laparoscopic colectomy was performed in 83 patients between November 2003 and April 2007. A total of 20 patients underwent laparoscopic colectomy with LOA and 53 patients underwent laparoscopic colectomy alone. Patients were prospectively followed to determine operative time (OT), blood loss, operative conversion, length of stay (LOS), and 30-day morbidity. RESULTS: Operative conversion was 2%, mean estimated blood loss (EBL) was 95+/-84 mL, and mean OT was 220+/-64 minutes. There were no anastomotic leaks or perioperative mortalities. There were 9 major complications (11%). Patients undergoing laparoscopic colectomy with LOA (n=20) compared with patients undergoing laparoscopic colectomy alone (n=63) had similar conversion rates (5% vs 2%), EBL (115+/-108 vs 88+/-74 mL), and major complications (15% vs 10%), but prolonged minor complications (25% vs 6%) and LOS (6.0+/-3.0 vs 4.6+/-1.5 days). CONCLUSIONS: Laparoscopic LOA combined with colectomy leads to similar conversion rates and major morbidity compared to laparoscopic colectomy alone.

Surgery for ulcerative colitis.

The type of surgery performed for UC varies from patient to patient and must take into account the nutritional status and health of the patient, the presence of dysplasia or cancer, the desire of the patient to maintain continence, the preoperative anorectal function, the degree of confidence in the diagnosis of UC, and the technical constraint because of certain body habituses. A total proctocolectomy is the surgical procedure of choice for UC. A restorative proctocolectomy is the preferred surgical approach that not only cures the patient of the disease and prevents the development of colorectal cancer, but also maintains continence with an improved quality of life.

Treatment of colon and rectal cancer.

During the past two decades, remarkable progress has been made in the treatment of cancers of the colon and rectum. Both oncologic and functional outcomes for this disease have improved dramatically. The reasons for the improved patient outcome in this disease include advances in knowledge of the biology of the disease, advances in surgical instrumentation and techniques, and ongoing advances in multimodality therapy, with the use of radiation and chemotherapy as an adjuvant to surgical resection. This review details many of these advances in a comprehensive manner and illustrates the necessity of a multidisciplinary approach for optimizing outcome for patients with these cancers.

Overexpression of the human inducible nitric oxide synthase gene enhances radiation-induced apoptosis in colorectal cancer cells via a caspase-dependent mechanism.

Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation.