Person:

Berger, David

Objectives: To determine the prevalence of incidentally found cases of gallbladder cancer, the incidence of residual disease at reexploration, and the changes in the mode of presentation, treatment, and survival of patients with gallbladder cancer during a period of more than 4 decades. Design: Retrospective case series. Setting: University-affiliated tertiary care center. Patients: Between January 1, 1962, and March 1, 2008, 402 patients with gallbladder cancer were identified and their clinicopathologic data were analyzed. Interventions: Surgical treatment, radiotherapy, and chemotherapy. Main Outcome Measures: Incidentally discovered gallbladder cancer, incidence of residual disease, and differences in presentation, treatment, and survival. Results: Surgical exploration was performed in 260 patients (64.7%), of whom 151 (58.1%) underwent resection. The median age of the patients was 72 years, and 72.3% were female. Between January 1, 1994, and March 1, 2008, 6881 laparoscopic cholecystectomies were performed, and there were 17 incidentally discovered cases of gallbladder cancer (0.25%). Residual disease on reexploration was identified in 0 of 2 patients with T1 tumor, 3 of 13 patients with T2 tumor, and 8 of 10 patients with T3 tumor (P = .01). Patients with stage IV disease (34 [13.1%] diagnosed from 1962-1979; 34 [13.1%] diagnosed from 1980-1997; and 22 [8.5%] diagnosed from 1998-2008) had a median survival of 4 months (range, 0-37 months). Concomitant liver resections increased in the third study period (11.1%, 10.1%, and 54.3%; P < .001), with an increase in negative margins (33.3%, 42.0%, and 63.0%; P = .01). Cox regression analysis identified T stage and surgical margin status as significant prognostic factors. Conclusions: Gallbladder cancer is incidentally found during 0.25% of laparoscopic cholecystectomies. As T stage increases, the likelihood of residual disease on reexploration increases. Although many patients with gallbladder cancer present with incurable disease and have very poor survival, the overall prognosis is improving, likely because of more extensive operations.

Background: The objective of this pilot study was to evaluate the feasibility and safety of natural orifice endoscopic transanal total mesorectal excision (TME) with laparoscopic assistance in a cohort study of five patients with stage I and IIA rectal cancer. Methods: Five eligible patients with node-negative rectal cancer located 4–12 cm from the anal verge were enrolled in an IRB-approved pilot study. All patients underwent transanal endoscopic TME with laparoscopic assistance, hand-sewn coloanal anastomosis, and a diverting loop ileostomy. Primary and secondary end points included adequacy of the mesorectal excision and 30-day postoperative complications, respectively. Results: Between November 2011 and May 2012, three males and two females underwent transanal endoscopic TME with laparoscopic assistance. Patient mean age and BMI were 48.6 ± 9.8 years and 25.7 ± 2.3 kg/m2, respectively. Tumors were located an average of 5.7 ± 2.4 cm from the anal verge and preoperatively staged as T1N0M0 (2), T2N0M0 (1), and T3N0M0 (2). Mean operative time was 274.6 ± 85.4 min with no intraoperative complications. Partial intersphincteric resection was performed in conjunction with transanal endoscopic TME in three patients. Pathologic examination of TME specimens demonstrated complete mesorectal excision in all cases with negative proximal, distal, and radial margins. Mean length of hospital stay was 5.2 ± 2.6 days and three minor complications occurred, including one ileus and two cases of transient urinary dysfunction. At a mean early follow-up of 5.4 ± 2.3 months, all patients remain disease-free. Conclusions: In this pilot study of five patients with rectal cancer, transanal endoscopic TME with laparoscopic assistance is feasible and safe, and is a promising alternative to open and laparoscopic TME. Evaluation of long-term functional and oncologic outcomes of this approach is needed before widespread adoption can be recommended.

Background: Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer. Methods: We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs). Results: A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest. Conclusions: After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis.

Peritoneal involvement is an important adverse prognostic factor in colorectal cancer (CRC) and determines a shift in the pathologic tumor node metastasis stage. Because peritoneal involvement is difficult to identify, use of special stains highlighting the peritoneal elastic lamina and mesothelial surface has been proposed. This study aims to determine whether use of elastic stain or CK7 immunohistochemistry on a single tissue section can refine the level of tumor invasion and determine whether restaging based on this assessment has prognostic significance in pT3N0 CRCs. Elastic stains were applied to 1 block per case from 244 consecutively resected pT3N0M0 CRCs. CK7 was evaluated in a 169-case subset. The elastic lamina was identified in only 101 cases (41%). Of those, 60 cases (24.6%) displayed elastic lamina invasion (ELI). This finding was associated with significantly worse (P<0.001) disease-free survival (DFS) (5-y DFS=60%) and significantly worse (P=0.01) overall survival (OS) (5-y OS=66.7%) compared with patients with no ELI (5-y DFS=87.8%, OS=92.7%) and those for whom no elastic lamina was identified (5-y DFS=82.5%, OS=86.0%). CK7 staining highlighted mesothelial cells in only 27 of 169 cases tested and helped demonstrate serosal invasion in only 5 cases (3%). In summary, the use of a single elastic stain is a useful and inexpensive method to demonstrate peritoneal involvement by tumor and should be considered for routine use in all pT3N0 CRCs. As tumors with ELI have an adverse prognosis, we propose that they should be upstaged compared with pT3N0 tumors without ELI.

Background: The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for gastric cancer incorporates the absolute number of metastatic lymph nodes (N status) and is optimally used when ≥15 nodes are examined. The ratio of metastatic to examined nodes (N ratio) is an effective prognostic tool, but has not been examined in Western patients undergoing primarily D1 lymphadenectomy. Methods: Two hundred and fifty seven patients with gastric adenocarcinoma who underwent gastric resection between 1995 and 2005 at our institution were examined. Novel N ratio intervals were determined using the best cutoff approach (Nr0: N ratio = 0 and ≥15 nodes examined; Nr1: 0 ≤ N ratio ≤ 0.3; Nr2: 0.3 < N ratio ≤ 0.7; and Nr3: N ratio > 0.7). Overall survival was examined according to N status and N ratio. Results: 83% of patients underwent D1 lymphadenectomy with a median of 14 lymph nodes examined. Overall survival stratified by N status was significantly different in patients with <15 nodes examined compared with those with ≥15 nodes examined. When we stratified by N ratio intervals, there was no significant difference in overall survival in patients with <15 versus ≥ 15 nodes examined. On multivariate analysis, N ratio but not N status was retained as an independent prognostic factor. Conclusions: The use of N status for staging patients undergoing primarily D1 lymphadenectomy results in significant stage migration due to varying numbers of nodes examined. Use of N ratio reduces stage migration and may be a more reliable method of staging these patients.

Background: Possible mass lesions identified on ultrasound (US) of the gallbladder may prompt an aggressive surgical intervention due to the possibility of a malignant neoplasm. Aim: This study aims to utilize a large modern series of patients with gallbladder lesions identified on US to evaluate imaging characteristics consistent with malignancy. Methods: A retrospective review was conducted of gallbladder ultrasound reports and clinicopathologic data of patients with a mass identified on US. Results: Approximately 59,271 abdominal ultrasounds and 9,117 cholecystectomies were performed between February 2000 and February 2010. We identified 213 patients with a questionable gallbladder neoplasm on ultrasonography who underwent surgical exploration. Median age was 52 years (range = 11–87 years) and 147 (69%) were females. Final pathology demonstrated no neoplasm in 130 patients (61%), while 32 patients (15%) had a wall adenomyoma, 36 (17%) had a polyp (five of which were malignant), 14 (7%) had an adenocarcinoma not arising from a polyp, and one patient had a cystic papillary neoplasm. The smaller the lesion, the more likely it was to be a pseudo-mass. For lesions measuring <5 mm on US, 83% had no lesion found on final pathology. Significant predictors of malignancy were age >52 years (p < 0.001), presence of gallstones on US (p = 0.004), size >9 mm (p < 0.001), evidence of invasion at the liver interface (p < 0.001), and wall thickening >5 mm (p < 0.001). Shape (sessile or penduculated), echogenicity (echogenic or isoechoic), or presence of flow on Doppler were not predictors of malignancy. An US size of ≤9 mm had a negative predictive value of 100% for malignancy. Conclusions: Despite improvements in imaging, most apparent lesions measuring <5 mm on US are not identified in the surgical specimen. US size >9 mm, age >52 years, US suggestion of invasion at the liver interface, and wall thickening >5 mm, especially in the presence of gallstones, should raise the suspicion of malignancy.

Objective: The purpose of this paper is to determine whether sites of distant recurrence are associated with specific locations of primary disease in colon cancer. Methods: A cohort including all patients (n = 947) undergoing a segmental colonic resection for colon cancer at our center (2004–2011) comparing site-specific metastatic presentation and recurrence rates, as well as their respective multivariable American Joint Committee on Cancer (AJCC) stage-adjusted hazard ratios (mHR). Results: Right-sided colectomies (n = 557) had a lower overall metastasis rate (24.8 % vs. 31.8 %; P = 0.017; mHR = 1.24 [95% CI: 0.96–1.60]; P = 0.011) due to significantly lower pulmonary metastasis in follow-up (2.7 % vs. 9 %; P < 0.001; mHR = 0.32 [95% CI: 0.17–0.58]; P = 0.001) and lower overall liver metastasis rate (15.6 vs. 22.1 %; P = 0.012; mHR = 0.74 [95% CI: 0.55–0.99];P = 0.050). Left colectomies (n = 127) had higher rates of liver metastasis during follow-up (9.4 % vs. 4.8 %; P = 0.029; mHR = 1.64 [95% CI: 0.86–3.15]; P = 0.134). Sigmoid resections (n = 238) had higher baseline rates of liver metastasis (17.1 % vs. 11.3 %; P = 0.015) and higher cumulative rates of lung (12.2 % vs. 5.4 %; P < 0.001; mHR = 2.26 [95 % CI: 1.41–3.63]; P = 0.001) and brain metastases (2.3 % vs. 0.6 %; P = 0.033; mHR = 4.03 [95% CI: 1.14–14.3]; P = 0.031). Other sites of metastasis, including the (retro) peritoneum, omentum, ovary, and bone, did not yield significant differences. Conclusions: Important variations in site-specific rates of metastatic disease exist within major resection regions of colon cancer. These variations may be important to consider when evaluating options for adjuvant treatment and surveillance after resection of the primary disease.

BACKGROUND:Colonoscopy has had a major impact on the incidence and survival of colon cancer for patients who are screened, usually beginning at the age of 50. Meanwhile, the incidence rate of colon cancer is actually increasing in the patients younger than 50 while no routine screening is implemented for this age group. METHODS:All patients surgically treated for colon cancer (2004-2011) without preexisting high-risk characteristics (hereditary nonpolyposis colorectal cancer, inflammatory bowel disease) were included (n = 1,015). Age-related disparities in baseline disease and outcomes were reviewed. RESULTS:Patients younger than 50 years of age (n = 108; 10.6%) had the greatest baseline rates of metastatic (20.4% vs 8.0%; P < .001), node-positive disease (54.6% vs 39.4%; P = .002), and greater rates of extramural vascular invasion (38.9 vs 29.4%; P = .043). Cancer-related mortality also was greatest in this group (28.7 vs 18.4%; P = .011). Multivariable Cox regression shows that patients younger than 50 are still at significantly greater risk of mortality after adjustment for effects of age, baseline AJCC staging, smoking, and comorbidity (hazard ratio: 1.57, 95% confidence interval 1.01-2.45; P = .049). DISCUSSION: Patients younger than 50 present with the most advanced and aggressive disease, giving them the worst stage-independent prognosis of all age groups. Potential causes include age-related differences in tumor biology and underdetection by current screening efforts. This raises the question of how to address the conundrum of the young colon cancer patient, who often is the proverbial needle in a haystack of young patients, with nonspecific gastrointestinal symptoms but who would benefit considerably from early detection.

Background: Emergency presentation with colon cancer is intuitively related to advanced disease. We measured its effect on outcomes of surgically treated colon cancer.

Methods: A retrospective cohort of 1,071 surgical colon cancer patients (2004 to 2011), with 102 emergency cases requiring surgery within the index admission, was analyzed.

Results: Emergency patients required longer surgeries (median 141 vs 124 minutes; P = .04), longer median admissions (8% vs 5%; P < .001), more readmissions (12.7% vs 7.1%; P = .040), and perioperative mortality (7.8% vs .8%; P < .001). Surgical pathology displayed higher rates of node-positive disease (56.6% vs 38.6%; P < .001), extramural vascular invasion (39.6% vs 29.1%; P = .021), and metastatic disease (19.6% vs 8%; P < .001). Consequently, adjusting for staging, emergency presentations had considerably higher mortality (odds ratio = 2.07; P = .003) and shorter disease-free survival (hazard ratio = 1.39; P = .042).

Conclusions: Emergency presentation is a stage-independent poor prognostic factor associated with aggressive tumor biology, resulting in longer surgeries and admissions, frequent readmissions, worsening outcomes, and increasing healthcare costs.

Importance: Screening colonoscopy seemingly decreases colorectal cancer rates in the United States. In addition to removing benign lesions and preventing progression to malignancy, screening colonoscopy theoretically identifies asymptomatic patients with early-stage disease, potentially leading to higher survival rates. Objectives: To assess the effect of screening colonoscopy on outcomes of colon cancer surgery by reviewing differences in staging, disease-free interval, risk of recurrence, and survival and to identify whether diagnosis through screening improves long-term outcomes in- dependent of staging. Design: Retrospective review of prospectively maintained, institutional review board-approved database. Setting: Tertiary care center with high patient volume. Patients: All patients who underwent colon cancer surgery at Massachusetts General Hospital from January 1, 2004, through December 31, 2011. Intervention: Colon cancer surgery. Main Outcomes and Measures: Postoperative staging, death, and recurrence, measured as incidence and time to event. Results: A total of 1071 patients were included, with 217 diagnosed through screening. Patients not diagnosed through screening were at risk for a more invasive tumor (≥T3: relative risk [RR]=1.96; P<0.001), nodal disease (RR=1.92; P<0.001), and metastatic disease on presentation (RR=3.37; P<0.001). In follow-up, these patients had higher death rates (RR=3.02; P<0.001) and recurrence rates (RR=2.19; P=0.004) as well as shorter survival (P<0.001) and disease-free intervals (P<0.001). Cox and logistic regression controlling for staging and base- line characteristics revealed that death rate (P=0.02) and survival duration (P=0.01) were better stage for stage with diagnosis through screening. Death and metastasis rates also remained significantly lower in tumors without nodal or metastatic spread (all P<0.001). Conclusions and Relevance: Patients with colon cancer identified on screening colonoscopy not only have lower-stage disease on presentation but also have better outcomes independent of their staging. Compliance to screening colonoscopy guidelines can play an important role in prolonging longevity, improving quality of life, and reducing health care costs through early detection of colon cancer.