Long-term outcomes by a transanal approach to total mesorectal excision for rectal cancer.

BACKGROUND: The challenge of performing a good total mesorectal excision (TME) dissection, particularly in the distal 1/3 of the rectum, has spurred interest in new techniques. Robotic surgery is advocated by some, and more recently, a "new" approach, the transanal total mesorectal excision, has been popularized to address this problem. While great interest in this technique exists, little long-term outcome data are available. We have been utilizing a transanal abdominal transanal approach to TME in order to facilitate the distal dissection, and here, we provide our long-term outcomes using this approach in the management of rectal cancer. METHODS: From a prospectively maintained rectal cancer database, we identified 373 consecutive rectal cancers treated with sphincter preservation surgery through a combined transanal and abdominal approach to TME. Perioperative, pathological, and oncologic outcomes were analyzed. RESULTS: Three hundred and seventy-three patients with rectal cancer underwent a transanally initiated TME with mean follow-up of 5.5 years. 91% of cancers were in the distal rectum. 68.9% were men and 53.2% of cancers were tethered or fixed on presentation. 97.7% received neoadjuvant radiotherapy (mean 5405 cGy, 5-fluorouracil based); average time from completion of neoadjuvant therapy to surgery was 11 weeks. 180 and 193 patients underwent completion of their operation through open and laparoscopic abdominal approaches. 96% of TME specimens were complete/near complete, 94% had a negative circumferential resection margin, and 98.6% had a negative distal margin. Perioperative morbidity and mortality rates were 13.4 and 0.3%. Overall local recurrence (LR), DM, and Kaplan-Meier 5-year actuarial survival were 7.4, 19.5, and 90%, respectively. CONCLUSION: This is the first report of long-term data using a transanal approach to TME supporting this approach for rectal cancer. Our data with 5-year follow-up show that adequate distal and circumferential margins with very good-quality TME specimens, and a low risk for LR with excellent overall survival can be achieved using this technique. Our long-term results support the promising reports of early experiences in the literature.

Post-ICU syndrome: Rescuing the undiagnosed.

Survivors of critical illness may develop postintensive care syndrome (PICS), a spectrum of conditions that include persistent cognitive dysfunction, acquired weakness, and intrusive memories akin to post-traumatic stress disorder. Relatively few ICU survivors are routinely followed in the outpatient setting by intensivists, but are regularly evaluated by primary care physicians and physician assistants in their practices. Specific and focused education about the key features of PICS, its effect on patients as well as family members, and potential therapeutic interventions may increase recognition of PICS and reduce its effect on survivors of critical illness.

Technique of last resort: characteristics of patients undergoing open surgery in the laparoscopic era.

BACKGROUND: The utilization rates for minimally invasive colorectal resection techniques (MICR) continue to increase. In some centers MICR methods are the preferred approach, however, open methods continue to be utilized for select patients. In this study, the profile and short-term outcomes of open colorectal resection (CR) and MICR patients are determined and compared. METHODS: A retrospective review of patients who underwent elective CR over 11 years at two institutions was performed. The MICR group contained both laparoscopic-assisted and hand-assisted cases. The past medical and surgical histories, indications, operations performed, and short-term outcomes were assessed. The Charlson co-morbidity index (CMI) was used to assess risk. RESULTS: During the study period 1080 patients underwent CR (Open, 141; MICR, 939). As judged by the CMI, there were more high-risk patients (score ≥2) in the Open group (34.38%) versus MICR (22.11%) p = 0.0029. Significantly more open patients had prior abdominal surgery and specifically CRs (Open, 15.60% vs. MICR, 2.13%, p < 0.001). Intraoperative transfusion (Open 25.7%; MICR 6.8%, p < 0.001) and diversion (25.53 vs. 11.50%, p < 0.001) were more common in the Open group. Not surprisingly, recovery of bowel function and length of stay were longer for the Open group. The overall complication rate was also higher for the Open patients (p < 0.001). CONCLUSION: When MICR is the procedure of choice, patients selected for Open CR are higher risk and more complex as judged by the CMI and past operative history. Not surprisingly, this translates into a longer length of stay, higher rates of transfusion, diversion, and complications. This disparity in patients undergoing CRs makes direct comparison of MICR and Open resection outcomes not reasonable.

Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma compositional changes.

BACKGROUND: Minimally invasive colorectal resection for cancer is associated with increased plasma levels of numerous proangiogenic proteins for 3 to 4 weeks postoperatively, and plasma from postoperative weeks 2 and 3 stimulates proangiogenic endothelial cell behavior in vitro. It is unknown if similar plasma changes occur after minimally invasive colorectal resection for benign pathology. OBJECTIVE: The aim of this study is to assess 1) plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 after minimally invasive colorectal resection for benign pathology and 2) postoperative plasma's effects on in vitro endothelial cell proliferation (branch point formation), migration, and invasion. DESIGN: Prospectively gathered plasma samples taken from patients undergoing colorectal resection who consented to participate in an institutional review board-approved plasma and data bank were used for ELISAs and in vitro endothelial cell studies. SETTINGS: The plasma and clinical data used were collected at 3 hospitals. PATIENTS: Patients undergoing minimally invasive colorectal resection for benign indications who were enrolled in a plasma/data bank and for whom adequate samples and volumes of plasma were available were included in the study. MAIN OUTCOME MEASURES: Perioperative plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were the primary outcomes measured. In vitro rates of endothelial cell branch point formation, migration, and invasion were determined after the addition of preoperative and postoperative plasma samples to endothelial cell cultures. RESULTS: Plasma from 86 patients undergoing minimally invasive colorectal resection for benign indications was assessed (diverticulitis, 30; benign polyps, 56). Plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were significantly increased for 3 to 4 weeks postoperatively compared with preoperative levels. In regard to the endothelial cell culture assays, significantly increased endothelial cell branch point formation, invasion, and migration results were noted with plasma from the second and third weeks postoperatively in comparison with preoperative culture results. LIMITATIONS: The weaknesses of this study are the limited numbers of late postoperative plasma samples and the need to bundle late samples into 7- to 12-day time blocks. CONCLUSIONS: Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma alterations similar to those found in patients who have cancer. Surgical trauma and not the indication is the likely cause.

The rate for the use of hand-assisted laparoscopic methods is directly proportional to body mass index.

BACKGROUND: Hand-assisted laparoscopic (HAL) colorectal resection remains controversial. Critics believe HAL methods lead to decreased use of laparoscopically assisted (LA) methods. Proponents believe selective HAL use increases minimally invasive surgery (MIS) use rates. This study assessed general and body mass index (BMI)-specific HAL and LA colorectal resection use by surgeons who embraced both methods. METHODS: This study retrospectively investigated 1,122 patients who underwent colorectal resection during an 8-year period. Surgical method, type of colorectal resection, BMI, comorbidities, incision length, and short-term outcomes were collected. RESULTS: The surgical methods included LA (60 %), HAL (25 %), and open (OP 15 %) procedures. The HAL group mean BMI was higher than that of the LA group (P < 0.0001), and the HAL use rate varied directly with BMI. The HAL technique was used for 48 % of the rectal, 36 % of the sigmoid, and 4 % of the right colorectal resections. The incision length was directly proportional to BMI for all the methods. Although the HAL incision lengths were significantly longer than the LA incision lengths for a BMI lower than 40 kg/m(2), there was no difference when the BMI was 40 kg/m(2) or higher. The comorbidities were greater in the HAL group than in the LA sigmoid colorectal resection group (P = 0.001). The mean hospital length of stay (LOS) was similar for the HAL and LA patients but longer for the open surgery patients (P < 0.0001 vs HAL group). The major complications, reoperations, and 30-day mortality rates were low and comparable. CONCLUSIONS: The HAL methods were used primarily for sigmoid and rectal colorectal resections and for higher BMI patients with more comorbidities. The mean incision length difference between the HAL and LA methods was 3.9 cm, but neither the LOS nor the major postoperative complications differed significantly. Selective use of HAL together with LA methods led to a MIS use rate of 85 % and facilitated MIS for high BMI patients. Together, the methods are complementary and may increase the number of minimally invasive surgeries performed.

The anxiogenic drug yohimbine activates central viscerosensory circuits in rats.

Systemic administration of the alpha(2)-adrenoceptor antagonist yohimbine (YO) activates the HPA stress axis and promotes anxiety in humans and experimental animals. We propose that visceral malaise contributes to the stressful and anxiogenic effects of systemic YO and that YO recruits brainstem noradrenergic (NA) and peptidergic neurons that relay viscerosensory signals to the hypothalamus and limbic forebrain. To begin testing these hypotheses, the present study explored dose-related effects of YO on food intake, conditioned flavor avoidance (CFA), and Fos immunolabeling in rats. Systemic YO (5.0 mg/kg BW, i.p.) inhibited food intake, supported CFA, and increased Fos immunolabeling in identified NA neurons in the ventrolateral medulla, nucleus of the solitary tract, and locus coeruleus. YO also increased Fos in the majority of corticotropin releasing hormone-positive neurons in the paraventricular nucleus of the hypothalamus. YO administered at 1.0 mg/kg BW did not inhibit food intake, did not support CFA, and did not increase Fos immunolabeling. Retrograde neural tracing demonstrated that neurons activated by YO at 5.0 mg/kg BW included medullary and pontine neurons that project to the central nucleus of the amygdala and to the lateral bed nucleus of the stria terminalis, the latter region receiving comparatively greater input by Fos-positive neurons. We conclude that YO produces anorexigenic and aversive effects that correlate with activation of brainstem viscerosensory inputs to the limbic forebrain. These findings invite continued investigation of how central viscerosensory signaling pathways interact with hypothalamic and limbic regions to influence interrelated physiological and behavioral components of anxiety, stress, and visceral malaise.

Viscerosensory activation of noradrenergic inputs to the amygdala in rats.

Norepinephrine (NE) acts in the amygdala to regulate processes underlying acquisition and expression of emotional learning. The present study investigated whether stimulation of gastric vagal sensory afferents activates neurons immunoreactive for the NE synthetic enzyme, dopamine beta hydroxylase (DbetaH), in medullary and pontine cell groups that innervate the central nucleus of the amygdala (CeA) in rats. To identify such neurons, retrograde neural tracers were microinjected bilaterally into the CeA. Seven to 10 days later, rats were injected intraperitoneally with saline vehicle (controls) or cholecystokinin octapeptide (CCK, 10 microgram/kg) to stimulate gastric vagal afferents, then perfused with fixative 60-90 min later. Brain sections were processed for localization of neural tracer and cFos protein (to identify activated cells). Approximately 30% of retrogradely labeled neurons in the nucleus of the solitary tract (NST, A2/C2 region) and 19% of retrogradely labeled neurons in the ventrolateral medulla (VLM, A1/C1 region) were activated in rats after CCK treatment. Triple immunolabeling of cFos, neural tracer, and DbetaH confirmed that the large majority of activated, CeA-projecting neurons were noradrenergic (or adrenergic). Conversely, CCK activated less than 4% of CeA-projecting neurons in the locus coeruleus (LC, A6 cell group), similar to control cases. These findings suggest that vagal afferent stimulation may modify amygdalar processes of emotional learning via direct noradrenergic/adrenergic projections from the caudal medulla to the CeA.

Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection.

AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer (CRC) and benign patients and postoperatively after CRC resection. METHODS: A plasma bank was screened for minimally invasive colorectal cancer resection (MICR) for CRC and benign disease (BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples (postoperative day 7-27) were available. Monocyte chemotactic protein-1 (MCP-1) levels (pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level (283.1, CI: 256.0, 294.3) was higher than the BEN group level (227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1 (446.3, CI: 418.0, 520.1), postoperative day 3 (342.7, CI: 320.4, 377.4), postoperative day 7-13 (326.5, CI: 299.4, 354.1), postoperative day 14-20 (361.6, CI: 287.8, 407.9), and postoperative day 21-27 (318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients (vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

Colorectal cancer in patients under 50 years of age: a retrospective analysis of two institutions' experience.

AIM: To investigate the epidemiological characteristics of colorectal cancer (CRC) in patients under 50 years of age across two institutions. METHODS: Records of patients under age 50 years of age who had CRC surgery over a 16 year period were assessed at two institutions. The following documents where reviewed: admission notes, operative notes, and discharge summaries. The main study variables included: age, presenting symptoms, family history, tumor location, operation, stage/differentiation of disease, and post operative complications. Stage of disease was classified according to the American Joint Committee on Cancer TNM staging system: tumor depth; node status; and metastases. RESULTS: CRC was found in 180 patients under age 50 years (87 females, 93 males; mean age 41.4 ± 6.2 years). Young patients accounted for 11.2% of cases during a 6 year period for which the full data set was available. Eight percent had a 1(st) degree and 12% a 2(nd) degree family CRC history. Almost all patients (94%) were symptomatic at diagnosis; common symptoms included: bleeding (59%), obstruction (9%), and abdominal/rectal pain (35%). Evaluation was often delayed and bleeding frequently attributed to hemorrhoids. Advanced stage CRC (Stage 3 or 4) was noted in 53% of patients. Most tumors were distal to the splenic flexure (77%) and 39% involved the rectum. Most patients (95%) had segmental resections; 6 patients had subtotal/total colectomy. Poorly differentiated tumors were noted in 12% and mucinous lesions in 19% of patients of which most had Stage 3 or 4 disease. Twenty-two patients (13%) developed recurrence and/or progression of disease to date. Three patients (ages 42, 42 and 49 years) went on to develop metachronous primary colon cancers within 3 to 4 years of their initial resection. CONCLUSION: CRC was common in young patients with no family history. Young patients with symptoms merit a timely evaluation to avoid presentation with late stage CRC.

Surgical residents' perception of the 16-hour work day restriction: concern for negative impact on resident education and patient care.

BACKGROUND: Effective July 1, 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted a 16-hour duty period limitation for postgraduate year I (PGY I) residents. Our aim was to assess the attitudes and perception of general surgery residents regarding the new duty hour limitation as well as the transfer of care process under the new guidelines. STUDY DESIGN: An anonymous, web-based survey was conducted nationally 7 months after the institution of the 16-hour duty limitation. RESULTS: A total of 464 completed surveys were analyzed. Overall, 75% of residents expressed dissatisfaction with the new duty hour limitation. PGY II to V residents reported a higher level of dissatisfaction compared with PGY I residents (87% vs 54%, p < 0.01). Eighty-nine percent of PGY II to V residents responded that there has been a shift of responsibilities from the PGY I class to PGY II to V residents, with 73% reporting increased fatigue as a result. Seventy-five percent of PGY I and 94% of PGY II to V residents expressed concerns about the adverse impact of the restrictions on the education of PGY I residents (p < 0.01). Residents at all PGY training levels reported encountering problems due to inadequate sign-outs (PGY I, 59%; PGY II to V, 85%; p < 0.01). Sixty-two percent of PGY I residents and 54% of PGY II to V residents believed that the new 16-hour duty restriction contributes to inadequate sign-outs (p = NS). Most PGY II to V residents (86%) believe there is a decreased level of patient ownership due to the work hour restrictions. CONCLUSIONS: The results of the survey suggest that the majority of general surgery residents are concerned over the potential negative impact of the duty limitation on resident education and patient care. Further research is needed to address these concerns.

Trimethylthiazoline supports conditioned flavor avoidance and activates viscerosensory, hypothalamic, and limbic circuits in rats.

Interoceptive stimuli modulate stress responses and emotional state, in part, via ascending viscerosensory inputs to the hypothalamus and limbic forebrain. It is unclear whether similar viscerosensory pathways are recruited by emotionally salient exteroceptive stimuli, such as odors. To address this question, we investigated conditioned avoidance and central c-Fos activation patterns in rats exposed to synthetic trimethylthiazoline (TMT), an odiferous natural component of fox feces. Experiment 1 demonstrated that rats avoid consuming novel flavors that previously were paired with TMT exposure, evidence that TMT supports conditioned flavor avoidance. Experiment 2 examined central neural systems activated by TMT. Odor-naive rats were acutely exposed to low or high levels of TMT or a novel nonaversive control odor and were perfused with fixative 60-90 min later. A subset of rats received retrograde neural tracer injections into the central nucleus of the amygdala (CeA) 7-10 days before odor exposure and perfusion. Brain sections were processed for dual-immunocytochemical detection of c-Fos and other markers to identify noradrenergic (NA) neurons, corticotropin-releasing hormone (CRH) neurons, and retrogradely labeled neurons projecting to the CeA. Significantly greater proportions of medullary and pontine NA neurons, hypothalamic CRH neurons, and CeA-projecting neurons were activated in rats exposed to TMT compared with activation in rats exposed to the nonaversive control odor. Thus the ability of TMT to support conditioned avoidance behavior is correlated with significant odor-induced recruitment of hypothalamic CRH neurons and brain stem viscerosensory inputs to the CeA.