Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival.

BACKGROUND: Few studies have simultaneously assessed the prognostic value of the multiple classification systems for lymph node (LN) metastases in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: In 600 patients with resected PDAC, we examined the association of LN parameters (AJCC 7th and 8th editions, LN ratio (LNR), and log odds of metastatic LN (LODDS)) with pattern of recurrence and patient survival using logistic regression and Cox proportional hazards regression, respectively. Regression models adjusted for age, sex, margin status, tumour grade, and perioperative therapy. RESULTS: Lymph node metastases classified by AJCC 7th and 8th editions, LNR, and LODDS were associated with worse disease free-survival (DFS) and overall survival (OS) (all Ptrend<0.01). American Joint Committee on Cancer 8th edition effectively predicted DFS and OS, while minimising model complexity. Lymph node metastases had weaker prognostic value in patients with positive margins and distal resections (both Pinteraction<0.03). Lymph node metastases by AJCC 7th and 8th editions did not predict the likelihood of local disease as the first site of recurrence. CONCLUSIONS: American Joint Committee on Cancer 8th edition LN classification is an effective and practical tool to predict outcomes in patients with resected PDAC. However, the prognostic value of LN metastases is attenuated in patients with positive resection margins and distal pancreatectomies.

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

BACKGROUND: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. METHODS: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. RESULTS: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. CONCLUSIONS: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.

A standardized method for endoscopic necrosectomy improves complication and mortality rates.

OBJECTIVES: Endoscopic necrosectomy is effective in the treatment of walled-off necrosis (WON), and is preferred to surgical approaches, however complication and mortality rates remain high with few centers regularly employing the technique. Lack of a standardized approach may also contribute to these limitations. METHODS: Prior to the study, a multidisciplinary team applied standardized care assessment and management plan principles to develop and optimize a systematic approach for the management of WON. Preoperative, postoperative, and endoscopic management were standardized. Patient preparation, room set-up, technical features (EUS-guidance, cold-access with balloon dilation, fragmentation of necrosis on the initial procedure, antibiotic lavage, double pigtail stents), and discontinuation of PPIs to encourage auto-digestion of necrosis were included. This study employed a consecutive prospective clinical registry to assess the clinical outcomes of this standardized approach. RESULTS: 60 consecutive patients underwent 1.58 ± 0.1 necrosectomies, with debridement accomplished on the initial procedure in 98.3%. 39 patients (65%) required only one session. Clinical resolution occurred in 86.7%, with radiologic confirmation. Percutaneous drainage was required in 8 patients during follow-up, and 4 of these later required surgery. Serious adverse events occurred in 3.3% of patients, and there was no mortality. CONCLUSIONS: The standardized technique employed in this series was associated with lower rates of adverse events, morbidity, and mortality than prior large series. Use of a systematic approach, and integrating elements of this method may improve the risk profile of endoscopic necrosectomy and allow broader adoption.

The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: more than 20,000 resections from the national cancer data base.

BACKGROUND: Operative mortality traditionally has been defined as the rate within 30 days or during the initial hospitalization, and studies that established the volume-outcome relationship for pancreatectomy used similar definitions. METHODS: Pancreatectomies reported to the National Cancer Data Base (NCDB) during 2007-2010 were examined for 30- and 90-day mortality. Unadjusted mortality rates were compared by type of resection, stage, comorbidities, and average annual hospital volume. Hierarchical logistic regression models generated risk-adjusted odds ratios for 30- and 90-day mortality. RESULTS: After 21,482 pancreatectomies, the unadjusted 30-day mortality rate was 3.7 % (95 % confidence interval [CI] 3.4-3.9 %), which doubled at 90 days to 7.4 % (95 % CI 7.0-7.8). The unadjusted and risk-adjusted mortality rates were higher at 30 days with increasing age, increasing stage, male gender, lower income, low hospital volume, resections other than distal pancreatectomy, Medicare or Medicaid insurance coverage, residence in a Southern census division, history of prior cancer, and multiple comorbidities. The lowest-volume hospitals (<5 per year) performed 19 % of the pancreatectomies, with a risk-adjusted odds ratios for mortality that were 4.2 times higher (95 % CI 3.1-5.8) at 30 days and remained 1.9 times higher (95 % CI 1.5-2.3) at 30-90 days compared with hospitals that had high volumes (≥40 per year). CONCLUSION: Mortality rates within 90 days after pancreatic resection are double those at 30 days. The volume-outcome relationship persists in the NCDB. Reporting mortality rates 90 days after pancreatectomy is important. Hospitals should be aware of their annual volume and mortality rates 30 and 90 days after pancreatectomy and should benchmark the use of high-volume hospitals.

Protecting patients from an unsafe system: the etiology and recovery of intraoperative deviations in care.

OBJECTIVE: To understand the etiology and resolution of unanticipated events in the operating room (OR). BACKGROUND: The majority of surgical adverse events occur intraoperatively. The OR represents a complex, high-risk system. The influence of different human, team, and organizational/environmental factors on safety and performance is unknown. METHODS: We video-recorded and transcribed 10 high-acuity operations, representing 43.7 hours of patient care. Deviations, defined as delays and/or episodes of decreased patient safety, were identified by majority consensus of a multidisciplinary team. Factors that contributed to each event and/or mitigated its impact were determined and attributed to the patient, providers, or environment/organization. RESULTS: Thirty-three deviations (10 delays, 17 safety compromises, 6 both) occurred--with a mean of 1 every 79.4 minutes. These deviations were multifactorial (mean 3.1 factors). Problems with communication and organizational structure appeared repeatedly at the root of both types of deviations. Delays tended to be resolved with vigilance, communication, coordination, and cooperation, while mediation of safety compromises was most frequently accomplished with vigilance, leadership, communication, and/or coordination. The organization/environment was not found to play a direct role in compensation. CONCLUSIONS: Unanticipated events are common in the OR. Deviations result from poor organizational/environmental design and suboptimal team dynamics, with caregivers compensating to avoid patient harm. Although recognized in other high-risk domains, such human resilience has not yet been described in surgery and has major implications for the design of safety interventions.

Endoscopic pyloric balloon dilatation obviates the need for pyloroplasty at esophagectomy.

BACKGROUND: Because the rate of acquired pyloric stenosis (APS) from truncal vagotomy is 15%, many surgeons perform pyloroplasty or pyloromyotomy at the time of esophagectomy. Endoscopic pyloric balloon dilatation (EPBD) is another method to manage APS. This study evaluated a cohort treated with preoperative EPBD. METHODS: This is a retrospective review of all patients treated with preoperative EPBD and esophagectomy for cancer from 2002 to 2009 at Brigham and Women's Hospital, a tertiary care center. Outcome measures included need for subsequent surgery for gastric outlet obstruction, rate of pyloric stenosis noted on postoperative endoscopy, and complications. RESULTS: Upon review of the series, 25 patients (80% male; median age, 63 [range 47-81] years) had outpatient preoperative EPBD and esophagectomies 1-2 weeks later and were included in the study. None had pyloroplasties or pyloromyotomies at the time of esophagectomy. Selected patients had postoperative endoscopy. Of the 25 patients, 20 had transhiatal esophagectomies, 3 had thoracoabdominal esophagectomies, and 2 had VATS 3-hole esophagectomies. Median follow-up time was 22 (range, 1-84) months. There were no complications from EPBD. There were no postoperative deaths. No patient needed a second operation for gastric outlet obstruction. All patients had postoperative barium swallows (BaS) or endoscopy or both. Only one patient (4%) required one postoperative EPBD to dilate a 16-mm pylorus. Three others had delayed gastric emptying on BaS with endoscopy showing each pylorus was wide open. Their symptoms improved with time. CONCLUSIONS: In this cohort, preoperative EPBD in all patients combined with postoperative EPBD in one patient obviated the need for pyloroplasty. This approach merits further study in a larger cohort, particularly to determine whether preoperative EPBD is necessary or if only selected postoperative EPBD is sufficient.

Pancreatic antegrade needle-knife (PANK) for treatment of symptomatic pancreatic duct obstruction in Whipple patients (with video).

BACKGROUND: Endoscopic decompression of symptomatic main pancreatic duct (MPD) dilation in Whipple patients is often difficult because of stenosis of the pancreaticojejunal (PJ) anastomosis. OBJECTIVE: To evaluate the feasibility and procedural safety of the pancreatic antegrade needle-knife (PANK) technique, with the goal of restoring antegrade MPD flow, when endoscopic retrograde pancreatography (ERP) and EUS-guided rendezvous fail. SETTING: Tertiary care center. DESIGN: Retrospective series. PATIENTS: Three patients with symptomatic MPD dilation refractory to ERP and EUS-guided rendezvous. INTERVENTIONS: Under EUS guidance, a 19-gauge echo-needle was used to gain access to the dilated MPD and a Jagwire advanced. After failed attempts at antegrade guidewire passage across the PJ stenosis, deep transgastric MPD access was achieved via a Soehendra stent retriever and balloon dilation. Careful antegrade needle-knife of the stenotic site was performed. A long pancreatic stent spanning the jejunum, MPD, and gastric access site was placed. Four to 8 weeks later, this stent was upsized and converted to a PJ stent, which in turn was removed 4 weeks thereafter. MAIN OUTCOME MEASUREMENTS: Technical feasibility and complications. RESULTS: All 3 patients successfully underwent the PANK procedure. Pre- and post-MRCP studies showed the mean MPD diameter decreased 60% from 8.3 mm to 3.6 mm (mean follow-up 8 months). At 24-month follow-up, all 3 patients experienced decreased or resolved pain without further need for MPD intervention. LIMITATIONS: Retrospective study with small numbers. CONCLUSIONS: When ERP and EUS rendezvous fail, the PANK procedure using a staged stent strategy seems to be an effective means of MPD decompression.

Cytology from pancreatic cysts has marginal utility in surgical decision-making.

BACKGROUND: Preoperative diagnosis of pancreatic cystic neoplasms is problematic. We evaluated our experience with endoscopic ultrasound (EUS) to determine the utility of fine-needle aspiration cytology (FNAC) in surgical decision-making. METHODS: Patients evaluated for pancreatic cysts with EUS fine-needle aspiration (FNA) from 3/1996-10/2003 were included. Patients undergoing both preoperative EUS-FNA and pancreatic resection were identified. FNAC read as a mucinous cystic neoplasm (MCN), suspicious for neoplasia, or mucinous epithelial/atypical cells were classified as "concerning." Cytology with no malignant cells was negative. FNAC read as indeterminate, atypical cells of undetermined significance, or possible contamination was nondiagnostic. RESULTS: Of 95 patients evaluated with EUS FNAC, 29 underwent resection. On final pathology, 7/29 lesions (24%) were malignant [two neuroendocrine tumors, three adenocarcinomas, one invasive intraductal papillary mucinous neoplasm (IPMN), and one metastatic uterine tumor], 4/29 (14%) were benign (three serous cystadenomas and one chronic pancreatitis), and 18/29 (62%) were premalignant (ten MCNs and eight IPMNs). Seven patients had concerning FNAC. All seven harbored malignant or premalignant lesions. Nine patients had negative FNAC: three (33%) with benign lesions and six (67%) with premalignant lesions. Thirteen of the 29 patients (45%) had nondiagnostic FNAC with 12/13 (92%) harboring a malignant or premalignant lesion. Sensitivity, specificity, positive predictive value, and negative predictive value were 28%, 100%, 100%, and 18%, respectively. CONCLUSION: The decision to proceed with nonoperative management should not be based on a negative or nondiagnostic FNAC alone, as 67% of negative and 92% of nondiagnostic specimens were associated with malignant or premalignant pathology.

Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance).

Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( Plogrank = .69; multivariable hazard ratio, 0.98; 95% CI, 0.78 to 1.24 comparing ECF with FU plus LV). Five-year disease-free survival rates were 39% in the FU plus LV arm and 37% in the ECF arm ( Plogrank = .94; multivariable hazard ratio, 0.96; 95% CI, 0.77 to 1.20). In post hoc analyses, the effect of treatment seemed to be similar across all examined patient subgroups. Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with standard FU and LV before and after radiotherapy.

Investigating Transitional Care to Decrease Post-pancreatectomy 30-Day Hospital Readmissions for Dehydration or Failure to Thrive.

BACKGROUND: Current literature emphasizes post-operative complications as a leading cause of post-pancreatectomy readmissions. Transitional care factors associated with potentially preventable conditions such as dehydration and failure to thrive (FTT) may play a significant role in readmission after pancreatectomy and have not been studied. METHODS: Thirty-one post-pancreatectomy patients, who were readmitted for dehydration or FTT between 2009 and 2014, were compared to 141 nonreadmitted patients. Medical record review and a questionnaire-based survey, specifically designed to assess transitional care, were used to identify predictors of readmissions for dehydration or FTT. Logistic regression models were used to evaluate outcomes. RESULTS: On multivariable analysis, the strongest predictors of readmission for dehydration and FTT were the patient's lower educational level (P = 0.0233), the absence of family during the delivery of discharge instructions (P = 0.0098), episodic intermittent nausea at discharge (P = 0.0019), uncertainty about quantity, quality, or frequency of fluid intake (P = 0.0137), and the inability or failure to adhere to the clinician's instructions in the outpatient setting (P = 0.0048). CONCLUSION: Transitional-care-related factors are found to be associated with post-pancreatectomy readmission for dehydration and FTT. Using these results to identify high-risk patients and implement focused preventive measures combining efficient communication and optimal inpatient and outpatient management could potentially decrease readmission rates.

Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus.

PURPOSE: Long-standing diabetes is a risk factor for pancreatic cancer, and recent-onset diabetes in the several years before diagnosis is a consequence of subclinical pancreatic malignancy. However, the impact of diabetes on survival is largely unknown. PATIENTS AND METHODS: We analyzed survival by diabetes status among 1,006 patients diagnosed from 1986 to 2010 from two prospective cohort studies: the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). We validated our results among 386 patients diagnosed from 2004 to 2013 from a clinic-based case series at Dana-Farber Cancer Institute (DFCI). We estimated hazard ratios (HRs) for death using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, smoking, diagnosis year, and cancer stage. RESULTS: In NHS and HPFS, HR for death was 1.40 (95% CI, 1.15 to 1.69) for patients with long-term diabetes (> 4 years) compared with those without diabetes (P < .001), with median survival times of 3 months for long-term diabetics and 5 months for nondiabetics. Adjustment for a propensity score to reduce confounding by comorbidities did not change the results. Among DFCI patient cases, HR for death was 1.53 (95% CI, 1.07 to 2.20) for those with long-term diabetes compared with those without diabetes (P = .02), with median survival times of 9 months for long-term diabetics and 13 months for nondiabetics. Compared with nondiabetics, survival times were shorter for long-term diabetics who used oral hypoglycemics or insulin. We observed no statistically significant association of recent-onset diabetes (< 4 years) with survival. CONCLUSION: Long-standing diabetes was associated with statistically significantly decreased survival among patients with pancreatic cancer enrolled onto three longitudinal studies.

Adenocarcinoma of the gastric cardia: what is the optimal surgical approach?

BACKGROUND: The incidence of adenocarcinoma of the gastric cardia is rising in Western countries. This study evaluates prognostic factors associated with surgical management of this cancer. STUDY DESIGN: Medical records of consecutive patients with gastric cardial cancer treated by surgical resection from 1991 through 2001 were reviewed. Survival was analyzed using the Kaplan-Meier method. Prognostic factors were evaluated using log-rank test and Cox regression. Mean followup period was 34 months. RESULTS: Eighty-two patients met study inclusion criteria. Median patient age was 65 years (range 86 to 22). Fifty-nine (72%) patients had type II tumors and 23 (28%) patients had type III tumors, according to the Siewert classification for gastroesophageal junction tumors. Twenty-seven (33%) patients underwent total esophagectomy, 24 (29%) patients underwent extended gastrectomy with thoracotomy, and 31 (38%) patients underwent extended gastrectomy without thoracotomy. Overall postoperative 5-year survival rate was 30%. On multivariate analysis, patient age 65 years and older, absence of lymph node metastasis, and R0 resection emerged as factors independently associated with improved postoperative survival. Frequency with which proximal resection margin was infiltrated with cancer was a function of gross margin length and T stage. Proximal gross margin length of at least 6 cm was required to achieve a microscopically negative proximal margin for T3 and T4 cancers. CONCLUSIONS: Achieving R0 resection should be the goal of surgical therapy for the gastric cardial cancer. The surgical approach should be tailored to individual patients to achieve this goal.

Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience.

The aim of this study was to evaluate contemporary outcomes associated with the management of gallbladder cancer. The medical records of 48 consecutive patients with gallbladder cancer treated at our institution from January 1981 through November 2001 were reviewed. Survival was analyzed using the Kaplan-Meier method (mean follow-up period 24 months) and the log-rank test. Prognostic factors were analyzed using Cox regression. Mean patient age was 68 years. Sixty percent of patients were female. Thirty-nine patients (81%) underwent laparotomy or laparoscopy. Eighteen patients (38%) underwent complete resection (10 simple cholecystectomies and 8 radical cholecystectomies). There were no procedure-related deaths. The overall 5-year survival rate was 13%. Patients who underwent complete resection had a higher 5-year survival rate (31%) than patients who underwent palliative surgery or no surgery (0%; P<0.05). For patients who underwent radical cholecystectomy, the 5-year survival rate was 60%. For the 18 patients who underwent curative resection, positive lymph node metastasis and patient age over 65 were factors predictive of significantly worse survival. Overall survival rates for patients with gallbladder cancer remain poor. Although radical surgery can be performed safely, it is associated with long-term survival only in a highly select subset of patients with gallbladder cancer.

Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer.

PURPOSE: In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. MATERIALS AND METHODS: Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy × 10. In dose level 2, patients received 5 Gy × 5 (every other day). In dose level 3, patients received 5 Gy × 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. RESULTS: With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. CONCLUSIONS: This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications.

Postgame analysis: using video-based coaching for continuous professional development.

BACKGROUND: The surgical learning curve persists for years after training, yet existing continuing medical education activities targeting this are limited. We describe a pilot study of a scalable video-based intervention, providing individualized feedback on intraoperative performance. STUDY DESIGN: Four complex operations performed by surgeons of varying experience--a chief resident accompanied by the operating senior surgeon, a surgeon with less than 10 years in practice, another with 20 to 30 years in practice, and a surgeon with more than 30 years of experience--were video recorded. Video playback formed the basis of 1-hour coaching sessions with a peer-judged surgical expert. These sessions were audio recorded, transcribed, and thematically coded. RESULTS: The sessions focused on operative technique--both technical aspects and decision-making. With increasing seniority, more discussion was devoted to the optimization of teaching and facilitation of the resident's technical performance. Coaching sessions with senior surgeons were peer-to-peer interactions, with each discussing his preferred approach. The coach alternated between directing the session (asking probing questions) and responding to specific questions brought by the surgeons, depending on learning style. At all experience levels, video review proved valuable in identifying episodes of failure to progress and troubleshooting alternative approaches. All agreed this tool is a powerful one. Inclusion of trainees seems most appropriate when coaching senior surgeons; it may restrict the dialogue of more junior attendings. CONCLUSIONS: Video-based coaching is an educational modality that targets intraoperative judgment, technique, and teaching. Surgeons of all levels found it highly instructive. This may provide a practical, much needed approach for continuous professional development.

Predictors of lymph node count in colorectal cancer resections: data from US nationwide prospective cohort studies.

OBJECTIVE: To identify factors that influence the total and negative lymph node counts in colorectal cancer resection specimens independent of pathologists and surgeons. DESIGN: We used multivariate negative binomial regression. Covariates included age, sex, body mass index, family history of colorectal carcinoma, year of diagnosis, hospital setting, tumor location, resected colorectal length (specimen length), tumor size, circumferential growth, TNM stage, lymphocytic reactions and other pathological features, and tumor molecular features (microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element 1 [LINE-1] methylation, and BRAF, KRAS, and PIK3CA mutations). SETTING: Two US nationwide prospective cohort studies. PATIENTS: Patients with rectal and colon cancer (N=918). MAIN OUTCOME MEASURES: The negative and total node counts (continuous). RESULTS: Specimen length, tumor size, ascending colon location, T3N0M0 stage, and year of diagnosis were positively associated with the negative node count (all P.002). Mutation of KRAS might also be positively associated with the negative node count (P=.03; borderline significance considering multiple hypothesis testing). Among node-negative (stages I and II) cases, specimen length, tumor size, and ascending colon location remained significantly associated with the node count (all P.002), and PIK3CA and KRAS mutations might also be positively associated (P=.03 and P=.049, respectively, with borderline significance). CONCLUSIONS: This molecular pathological epidemiology study shows that specimen length, tumor size, tumor location, TNM stage, and year of diagnosis are operator-independent predictors of the lymph node count. These crucial variables should be examined in any future evaluation of the adequacy of lymph node harvest and nodal staging when devising individualized treatment plans for patients with colorectal cancer.

Surgery and staging of pancreatic neuroendocrine tumors: a 14-year experience.

BACKGROUND: The aims of this study were to evaluate contemporary outcomes associated with the surgical management of pancreatic neuroendocrine tumors (PNETs) and to assess the prognostic value of the World Health Organization (WHO) classification and TNM staging for PNETs. METHODS: The medical records of 73 consecutive patients with PNETs treated at a single institution from January 1992 through September 2006 were reviewed. Survival was analyzed with the Kaplan-Meier method (median follow-up: 43 months). RESULTS: Median patient age was 52 years (range, 19-83 years), and 36 (49%) patients were male. Thirty-three patients had a well-differentiated neuroendocrine tumor (WDT), 26 had a well-differentiated neuroendocrine carcinoma (WDCa), and 14 had a poorly differentiated neuroendocrine carcinoma (PDCa). Fifty (68%) patients underwent potentially curative resection, and the 5-year disease-specific survival (DSS) rate for the entire cohort was 62%. WHO classification and TNM staging system provided good prognostic stratification of patients; 5-year DSS rates were 100% for WDT, 57% for WDCa, 8% for PDCa, respectively, by WHO classification (p < 0.001), and 100% for stage 1, 90% for stage 2, 57% for stage 3, and 8% for stage 4, respectively, by TNM stage (p < 0.001). Among the patients who underwent potentially curative resection, nodal status, distant metastasis, and tumor grade were significant prognostic factors. CONCLUSION: WHO classification and TNM staging are useful for prognostic stratification among patients with PNETs.

Severe acute gastrointestinal graft-vs-host disease: an emerging surgical dilemma in contemporary cancer care.

OBJECTIVE: To determine the natural history of and guidelines for the surgical management of severe acute gastrointestinal (GI) graft-vs-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). DESIGN: Case series from a prospective database. SETTING: Tertiary care referral center/National Cancer Institute-designated Comprehensive Cancer Center. PATIENTS: A total of 63 of 2065 patients (3%) undergoing HSCT for hematologic malignancies from February 1997 to March 2005 diagnosed clinically with severe (stage 3 or 4) acute GI GVHD. Main Outcome Measure Percutaneous or surgical intervention. Perforation, obstruction, ischemia, hemorrhage, and abscess were considered surgically correctable problems. RESULTS: Severe acute GI GVHD was diagnosed in 63 patients (median age at HSCT, 47.6 years) at a median of 23 days after HSCT. Clinical diagnosis was confirmed histologically in 84% of patients. On computed tomography and/or magnetic resonance images, 64% had bowel wall thickening, 20% had a normal-appearing bowel, and 16% had nonspecific findings; none had evidence of perforation, obstruction, or abscess. All were initially treated with immunosuppression. Only 1 patient (1.6%) required intervention, undergoing a nontherapeutic laparotomy for worsening abdominal pain. A total of 83% of patients have died (median time to death from HSCT, 119 days; from GI GVHD diagnosis, 85 days). None who underwent an autopsy died of a surgically correctable cause. CONCLUSIONS: This series represents a large single-center experience with GI GVHD reviewed from a surgical perspective. Operative intervention was rarely required. Therefore, mature surgical judgment is necessary to confirm the absence of surgically reversible problems, thus avoiding unnecessary operations in this challenging patient population.