Overview of Personalized Medicine in GI Cancers

Cancer biomarkers may be used for prevention (identification of patients at high risk for cancer), estimating prognosis and/or repsonse to conventional chemotherapies, or guide the use of specific targeted therapies. This overview provides examples in each category for gastrointestinal cancers and reviews current concepts in personalized medicine.     

Incidence of Urogenital Cancers in Gunma Prefecture, Japan: A 10-Year Summary

Background : Although the incidence of urogenital cancers in Japan is lower than that of other cancers, it is increasing steadily. Thus, an epidemiologic study was necessary to determine the measures that would decrease the mortality rate associated with these cancers.
Methods : The subjects were 4759 patients with urogenital cancer who were living in Gunma Prefecture and who were newly diagnosed between 1985 and 1994. The data were analyzed by year and by patients' ages. The incidence rates of each disease were expressed as the number of cases per 100,000/year, and age-adjusted rates were adjusted to the world population.
Results : The number of males and females afflicted by urogenital cancers increased over the 10-year period. The increase in age-adjusted incidence rates was sharpest for prostate, renal cell, and testicular cancers among males, and for renal cell, renal pelvic and ureter cancers among females. When age-specific rates were plotted against age on double logarithmic scales, the cancers were classified as type 1 (linear), type 2 (linear until a certain age, then flattening out or decreasing), or type 3 (irregular) based on the slope of the line. The magnitude of increase in the age-specific incidence rates of type 1 cancers with age was on the order of the 12th power for prostate cancer and the 5th power for bladder cancer. When the 10 years were divided into 2 periods (earlier and later), the age-specific incidence rates of prostate and renal cell cancers increased in all age groups, whereas the age-specific incidence rates of cancers that increased less sharply remained stable or even declined in some age groups.
Conclusion : These epidemiologic data should be useful in reducing the mortality rates associated with these cancers.     

Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance: a Systematic Review by the Testicular Cancer Guidelines Panel

Context

Patients with clinical stage I (CS I) seminoma testis with large primary tumours and/or rete testis invasion (RTI) might have an increased risk of relapse. In recent years, these risk factors have frequently been employed to decide on adjuvant treatment.

全直肠系膜切除术治疗直肠癌95例临床分析

目的探讨全直肠系膜切除术（total mesorectal excision,TME）治疗直肠癌的临床疗效。方法回顾性分析2003年1月至2006年1月,对95例中低位直肠癌患者行TME术治疗的临床资料,其中54例行Dixon术,8例行Parks术,33例行Miles术。结果全组病例无手术死亡。术后吻合口漏3例,吻合口狭窄2例,吻合口出血2例。在获得随访1～6年的91个病例中,性功能障碍21．9％（20／91）,局部复发7．7％（7／91）,其中吻合口复发1．1％（1／91）。结论直肠癌术中TME可明显降低直肠癌术后局部复发率,减少性功能障碍发生。     

Evaluation of an intensive strategy for follow-up and surveillance of primary breast cancer

Background: Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist. Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies, including chest radiographs, bone scans, and CT scans, whereas others have established a minimalist approach consisting of only history, physical examinations, and mammograms. Objectives: Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival. Methods: During a 10-year period (1986–1996), 129 patients with recurrent disease were identified from a prospective database of 1898 breast cancer patients. The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection. Results: Twenty-seven of 126 (21%) patients were assigned to the intensive method of detection group (LFT, CEA, CA 15-3, chest radiograph, CT scan, and bone scan); 99 of 126 (79%) patients were assigned to the minimal detection group (history, physical examination, and mammography). Distant disease to the bone was the most common initial tumor recurrence, at 27%. History, physical examination, and mammography detected recurrent cancer in approximately the same amount of time as LFTs, tumor markers, CT scans, and chest radiographs (P=.960). When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence, there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P=.95). The independent variables age, tumor size, type of surgery, number of positive nodes, time to recurrence, method of detection, and site of recurrence (regional or distant) were subject to univariate and multivariate analysis by the Cox proportional hazards model. Only two variables had an impact on survival by multivariate analysis: early timing of the recurrence (P=.0011) and the site of the recurrence (P=.02). Timing was defined as early (⩽365 days from the time of diagnosis to recurrence) or late (⩾365 days from the time of diagnosis to recurrence). Early recurrence was the first variable found to be significant on stepwise forward regression analysis. The primary site of recurrence was significant at step two. The method of detection—intensive or minimal—did not significantly affect survival (P=.18). Conclusions: There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. Expensive diagnostic tests such as bone scans, CT scans, and serial tumor markers are best used for detection of metastasis in symptomatic patients.     

The utility of routine postoperative upper GI series following laparoscopic gastric bypass

Background Routine upper gastrointestinal (UGI) studies following laparoscopic Roux-en-Y gastric bypass (LRYGBP) have the potential advantage of early identification of anastomotic complications. The aim of our study was to evaluate the efficacy of routine postoperative UGI and its relationship to clinical outcomes. Methods Over a three-year period, 516 patients underwent LRYGBP followed by routine postoperative UGI studies. Data were collected on the results of the UGI, clinical parameters, and patient outcomes. Study groups were composed of patients with a normal UGI (Group I, n = 455), abnormal UGI not requiring further intervention (Group II, n = 36), and abnormal UGI requiring further intervention (Group III, n =25). Statistical significance was set at α= 0.05 level for all analyses. Results The three study groups were not statistically different in mean age (42 years) or body mass index (BMI) (45) and were predominantly female (90%). Most patients had an uneventful postoperative course. Anastomotic complications (gastrojejunostomy and jejunojejunostomy) were uncommon (1.3%). The sensitivity of the UGI for anastomotic leak in this study was low (33%). However, all patients with alimentary limb obstruction (n = 3) had UGI evidence of this complication. Of the 516 UGI reports, there were only 25 (4.8%, Group III) that were abnormal and required some form of intervention ranging from serial imaging (84%) to reoperation (16%). Of the various clinical parameters examined, the patients in Group III demonstrated a significantly higher prevalence of fever (p < 0.001), tachycardia (p < 0.01), vomiting (p < 0.001), and postoperative day 1 leukocytosis (p < 0.005). Conclusions Our data suggest that routine UGI after LRYGBP has limited utility as it may result in unnecessary intervention based on false-positive results or a delay in treatment based on false-negative results. We advocate selective UGI imaging following LRYGBP based on the patient’s clinical factors, particularly fever and tachycardia. Poster presentation at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Las Vegas, Nevada, April 2007     

The clinic factors in evaluating long-term outcomes of patients with stage I colorectal cancer

BackgroundThis study aimed to explore the survival and recurrences of stage I colorectal cancer (CRC) patients. Through the analysis of the results of preoperative serological values, we seek to find factors associated with the survival and recurrence of patients with stage I CRC.MethodsWe retrospectively enrolled patients from 2012 January to 2015 April. Survival rates were calculated with the Kaplan–Meier method and survival curves were compared using the log-rank test. The independent prognostic factors were assessed by the Cox proportional hazard regression analysis.ResultsA total of 476 patients with stage I disease were included to analysis. Median follow-up was 68 months (4–84 months) for OS. The OS rates were related to age,CEA, CHOL, LDL-C levels,HBDH, WBC, NLR, LMR, LWR, PNI, SII, NPS and CONUT at univariate analysis. At multivariate analysis, age, WBC and SII were confirmed to be independent prognostic factors for OS. The median DFS was 68 months (2–84 months). In this period, 38 (8.0%) experienced tumor relapse, and 17 (44.7%) died due to recurrence. The DFS rates were related to higher CEA, higher NLR values and lower LMR values at univariate analysis. At multivariate analysis, just elevated CEA levels was confirmed to be independent prognostic factors.ConclusionsPatients with stage I colorectal cancers still have a clinically significant risk of recurrence. We still need to expand the number of cases to validate our findings and better identify patients who are at high risk of relapse with less severe disease.     

Updated Hysterectomy Surveillance and Factors Associated With Minimally Invasive Hysterectomy

Background and Objectives:

The goal of this study is to obtain updated surveillance statistics for hysterectomy procedures in the United States and identify factors associated with undergoing a minimally invasive approach to hysterectomy.

Methods:

A cross-sectional analysis of the 2009 United States Nationwide Inpatient Sample was performed. Subjects included all women aged 18 years or older who underwent hysterectomy of any type. Logistic regression and multivariate analyses were performed to assess the proportion of hysterectomies performed by various routes, as well as factors associated with undergoing minimally invasive surgery (laparoscopic, vaginal, or robotic).

Results:

A total of 479 814 hysterectomies were performed in the United States in 2009, 86.6% of which were performed for benign indications. Among the hysterectomies performed for benign indications, 56% were completed abdominally, 20.4% were performed laparoscopically, 18.8% were performed vaginally, and 4.5% were performed with robotic assistance. Factors associated with decreased odds of a minimally invasive hysterectomy included the following: minority race (P < .0001), fibroids (P < .0001), concomitant adnexal surgery (P < .0001), self-pay (P = .01) or Medicaid as insurer (P < .0001), and increased severity of illness (P < .0001). Factors associated with increased odds of a minimally invasive hysterectomy included the following: age >50 years (P < .0001), prolapse or menstrual disorder (P < .0001), median household income of $48 000–$62 999 (P = .007) or ≥$63 000 (P = .009), and location in the West (P = .02). A length of stay >1 day was most common in abdominal hysterectomy cases (96.1%), although total mean charges were highest for robotic cases ($38 161).

Conclusion:

The US hysterectomy incidence in 2009 decreased from prior years'' reports, with an increasing frequency of laparoscopic and robotic approaches. Racial and socioeconomic factors influenced hysterectomy mode.     

Heterogeneity in Surveillance after Endovascular Aneurysm Repair in the UK

Objectives

Surveillance after Endovascular Aneurysm Repair (EVAR) is considered mandatory, but the optimal regimen remains controversial. The aim of the present study was to report the nature of routine post-EVAR surveillance protocols in the UK, in order to identify the degree of variation in national practice and from the manufacturer’s instructions for use (IFU).

Methods

A telephone survey was administered to 41 centres with 10 years’ experience in EVAR to identify their standard surveillance protocol after EVAR. Data were collected regarding the number of surveillance CT or ultrasound performed up to 5 years postoperatively.

Results

12/41 centres used CT as the primary mode of surveillance, 14/41 centres used USS as the primary mode of surveillance, and 15/41 centres used a combination of CT and USS. The mean ± s.d. number of CT scans performed cumulatively up to 1 year and 5 years post surgery were 1.1 ± 0.6 and 3.5 ± 2.9 respectively. The mean ± s.d. ultrasound scans performed at 1 year and 5 years post surgery were 0.5 ± 0.9and 4.7 ± 3.6 respectively.

Conclusions

Significant heterogeneity exists in surveillance after EVAR in the UK. Efforts should be made to establish consensus towards a national surveillance protocol.     

Assessment of risk-independent follow-up to detect asymptomatic recurrence after curative resection of colorectal cancer

Background and aims Colorectal cancer is one of the leading causes of cancer death. We analyzed the value of standardized, risk-independent postoperative surveillance.Materials and methods Between 1995 and 2001, 564 patients with colorectal cancer underwent standardized oncologic resection. One hundred thirty-four were unable to take part in the surveillance program, while 430 patients were grouped as follows: group I (n=272, risk-independent follow-up), group II (n=113, follow-up at other departments), and group III (n=45, no follow-up).Results The 5-year cancer-specific survival rate for UICC III and IV was significantly higher in group I (87%) as compared to group II (35%). In group I, the 5-year disease-free survival rate was 70%. Cancer recurrence occurred at mean 17 (±12) months after colorectal resection and yielded a 5-year survival rate of 63%. Reresection was performed in 17 (35%) patients, of whom ten remained disease-free (5-year survival rate, 91%). The money spent for one patient’s 5-year follow-up was 1665.Conclusions A standardized, risk-independent follow-up program allows early diagnosis of asymptomatic recurrence of colorectal cancer. Reresection improves the 5-year survival rate in this setting.Presented at the Tripartite Colorectal Meeting, Dublin, July 2005 and at the Congress of the German Society of Surgery, Munich, April 2005     

No Role for Routine Chest Radiography in Stage I Seminoma Surveillance

Background

After orchidectomy, the standard management options available for stage I seminoma are surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. The optimal follow-up protocol for surveillance is yet to be determined but includes frequent chest radiography (CXR) and computed tomography (CT) scan of the abdomen and pelvis (CT-AP).

Objective

The purpose of this study was to identify the modality that first detected relapse and to assess the value of the CXR in this setting.

Design, setting, and participants

Five hundred twenty-seven patients with histologically confirmed stage I testicular seminoma were managed with surveillance at our institution between 1982 and 2005. Routine CXRs were performed with each CT-AP and were done every 4–6 mo for 7 yr and annually thereafter. The median follow-up was 72 mo (range: 1–193).

Measurements

Measurements included the 5-yr relapse rate, overall survival, and disease-free survival to determine the modality that first detected relapse disease.

Results and limitations

The 5-yr actuarial relapse rate for the 527 patients was 14%. The 5-yr disease-free survival and overall survival were 85.7% and 98.6%, respectively. Seventy-three patients (97.3%) had an abnormal CT-AP and a normal CXR at relapse. One patient (1.3%) had an abnormal CT-AP with pulmonary metastasis on CXR and CT chest scan, and one patient (1.3%) had a biopsy-proven inguinal node metastasis with a normal CXR. No patient had a normal CT-AP or physical examination with an abnormal CXR at relapse. This is a single-center retrospective study based on a relatively small number of relapses and may be subject to bias. Confirmation of these results from other studies would be useful for wider clinical applicability.

Conclusions

All except one relapse were detected by CT-AP with no relapses detected on CXR alone; therefore, CXR may be omitted as routine imaging in surveillance protocols.     

Mammography and the Risk of Thyroid and Hematological Cancers: A Nationwide Population‐based Study

To investigate the association between thyroid cancer as well as the most radiosensitive hematological cancers and radiation exposure from mammography. This study used information from a random sample of two million persons enrolled in the nationally representative Taiwan National Health Insurance (NHI) Research Database. The exposed group was composed of women aged 18–65 who had undergone diagnostic mammography between 2000 and 2007. The nonexposed control group was composed of women in the NHI database who had never undergone diagnostic mammography. There were 25,362 women in the exposed group and 203,317 women in the nonexposed group. After adjusting for age and comorbidities, the patients who had been exposed to radiation from mammography did not have a significantly higher risk of developing thyroid cancer and hematological cancers (adjusted HR, 1.201; 95% CI, 0.813–1.774 for thyroid cancer and adjusted HR, 1.228; 95% CI, 0.838–1.800 for hematological cancers). The scattered radiation dose delivered by mammography should be cautiously handled, but no additional concerns about the risk of thyroid cancer developing malignancy should be emphasized.     

Considerations on the use of diagnostic markers in management of patients with bladder cancer

Although the incidence of bladder cancer lags behind that of other malignancies, it has the highest rate of recurrence among all US malignancies. The propensity to recur and the possibility of disease progression require aggressive surveillance, which has led to bladder cancer being the most expensive malignancy to treat in the United States. Current non-tailored surveillance strategies applied uniformly to all patients with non-muscle invasive bladder cancer may impose excessive diagnostic burden on patients with low-grade disease for the sake of adequately monitoring those with potentially aggressive disease. The recent identification of several bladder cancer tumor markers has led to attempts to determine if these markers can enhance existing surveillance strategies by possibly tailoring surveillance strategies to individual patients. These markers may result in cost savings by properly identifying which patients can safely delay cystoscopy and which patients require more periodic assessment. Furthermore, we may be able to identify those patients with “occult disease” that require more invasive assessments and earlier aggressive treatment. We will review diagnostic considerations in the use of these markers for the detection of recurrent bladder cancer and summarize the benefits and costs of the more promising bladder cancer markers.     

Long-term Risk of Recurrence in Surgically Treated Renal Cell Carcinoma: A Post Hoc Analysis of the Eastern Cooperative Oncology Group—American College of Radiology Imaging Network E2805 Trial Cohort

Currently, surveillance guidelines following surgical resection of clinically localized renal cell carcinoma (RCC) are clear within the first 5 yr; however, these lack the same degree of objectivity following this cutoff. We sought to investigate the long-term risk of recurrence in surgically treated RCC in order to determine the utility of long-term surveillance. A post hoc analysis of patients within the Eastern Cooperative Oncology Group—American College of Radiology Imaging Network (ECOG-ACRIN) E2805 trial cohort was performed. The 36-mo cumulative incidence of recurrence was assessed at set intervals following surgery, in order to dynamically assess recurrence through the use of a conditional survival model. Of the 1943 patients included in the original cohort, 730 developed recurrence. The 36-mo cumulative incidences of recurrence were found to be 31%, 26%, 19%, 16%, 19%, and 20% for patients at 0, 12, 24, 36, 48, and 60 mo from surgery, respectively. At 0 mo from surgery, age, pathological T3/4 stage (hazard ratio [HR] = 1.56), pathological N1/2 stage (HR = 2.38), and Fuhrman grades 3 and 4 (HR = 1.36 and HR = 2.41, respectively) were independent predictors of recurrence; however, this was not seen at 60 mo following surgery. These findings support that surveillance imaging should be performed beyond 5 yr following surgical resection of intermediate- to high-risk RCC.Patient summary: Follow-up for surgically resected localized renal cell carcinoma should be performed beyond 5 yr, for the rates of recurrence remain significant beyond this 5 yr endpoint.