Trends in Distal Esophageal and Gastroesophageal Junction Cancer Care: The Dutch Nationwide Ivory Study.

OBJECTIVE: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer. SUMMARY OF BACKGROUND DATA: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer. METHODS: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods. RESULTS: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% ( P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027). CONCLUSION: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

OBJECTIVE: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. BACKGROUND: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. METHODS: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. RESULTS: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84). CONCLUSIONS: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

Reasons for low uptake of a psychological intervention offered to cancer survivors with elevated depressive symptoms.

OBJECTIVE: In line with screening guidelines, cancer survivors were consecutively screened on depressive symptoms (as part of standard care), with those reporting elevated levels of symptoms offered psychological care as part of a trial. Because of the low uptake, no conclusions could be drawn about the interventions' efficacy. Given the trial set-up (following screening guidelines and strict methodological quality criteria), we believe that this observational study reporting the flow of participation, reasons for and characteristics associated with nonparticipation, adds to the debate about the feasibility and efficiency of screening guidelines. METHODS: Two thousand six hundred eight medium- to long-term cancer survivors were consecutively screened on depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Those with moderate depressive symptoms (PHQ-9 ≥ 10) were contacted and informed about the trial. Patient flow and reasons for nonparticipation were carefully monitored. RESULTS: One thousand thirty seven survivors (74.3%) returned the questionnaire, with 147 (7.6%) reporting moderate depressive symptoms. Of this group, 49 survivors (33.3%) were ineligible, including 26 survivors (17.7%) already receiving treatment and another 44 survivors (30.0%) reporting no need for treatment. Only 25 survivors (1.0%) participated in the trial. CONCLUSION: Of the approached survivors for screening, only 1% was eligible and interested in receiving psychological care as part of our trial. Four reasons for nonparticipation were: nonresponse to screening, low levels of depressive symptoms, no need, or already receiving care. Our findings question whether to spend the limited resources in psycho-oncological care on following screening guidelines and the efficiency of using consecutive screening for trial recruitment in cancer survivors.

The interplay between partners' responsiveness and patients' need for emotional expression in couples coping with cancer.

The central aim of this longitudinal observational study was to test whether patients with a high need for emotional expression are especially sensitive to their partners' responsive behavior, and therefore at risk for depressive symptoms when responsiveness is withheld. Patients with colorectal cancer and their partners (n = 58) participated in a longitudinal study (3, 5 and 9 months after the diagnosis). Additionally to self-report measurements (i.e., patients' need for emotional expression, patients' depressive symptoms and patients' relationship satisfaction) couples were videotaped discussing cancer-related concerns. External observers coded partners' responsiveness (i.e., understanding, validation and caring) and patients' self-disclosures. Partner responsiveness predicted lower levels of depressive symptoms over time in patients who had a relatively high need for emotional expression above and beyond the effect of relationship satisfaction. We demonstrated that partners' understanding and validation are more important in explaining patients' depressive symptoms than partners' caring behavior. Our findings highlight the importance of the relational context in improving adaptation to cancer taking into account individual differences.

Underuse of long-term routine hospital follow-up care in patients with a history of breast cancer?

BACKGROUND: After primary treatment for breast cancer, patients are recommended to use hospital follow-up care routinely. Long-term data on the utilization of this follow-up care are relatively rare. METHODS: Information regarding the utilization of routine hospital follow-up care was retrieved from hospital documents of 662 patients treated for breast cancer. Utilization of hospital follow-up care was defined as the use of follow-up care according to the guidelines in that period of time. Determinants of hospital follow up care were evaluated with multivariate analysis by generalized estimating equations (GEE). RESULTS: The median follow-up time was 9.0 (0.3-18.1) years. At fifth and tenth year after diagnosis, 16.1% and 33.5% of the patients had less follow-up visits than recommended in the national guideline, and 33.1% and 40.4% had less frequent mammography than recommended. Less frequent mammography was found in older patients (age > 70; OR: 2.10; 95%CI: 1.62-2.74), patients with comorbidity (OR: 1.26; 95%CI: 1.05-1.52) and patients using hormonal therapy (OR: 1.51; 95%CI: 1.01-2.25). CONCLUSIONS: Most patients with a history of breast cancer use hospital follow-up care according to the guidelines. In older patients, patients with comorbidity and patients receiving hormonal therapy yearly mammography is performed much less than recommended.

A longitudinal comparison of arm morbidity in stage I-II breast cancer patients treated with sentinel lymph node biopsy, sentinel lymph node biopsy followed by completion lymph node dissection, or axillary lymph node dissection.

BACKGROUND: Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and ALND in stage I/II breast cancer patients. MATERIALS AND METHODS: Breast cancer patients who had SLNB (n = 51), SLNB + CLND (n = 55), and ALND (n = 65) were physically examined 1 day before surgery (T0), and after 6 (T1), 26 (T2), 52 (T3), and 104 (T4) weeks. Differences in 8 parameters between the affected and unaffected arms were calculated. General linear models were computed to examine time, group, and interaction effects. RESULTS: All outcomes changed significantly, mostly nonlinearly, over time (T0-T4). Between T1 and T4, limitations decreased in abduction (all groups); anteflexion, abduction-exorotation, abduction strength (SLNB + CLND, ALND); flexion strength (SLNB + CLND); and arm volume (SLNB, SLNB + CLND). At T4, limitations in anteflexion (SLNB, ALND), abduction (SLNB + CLND, ALND), exorotation (ALND), abduction-exorotation (all groups), and volume (SLNB + CLND, ALND) increased significantly compared with T0. The SLNB group showed an advantage in anteflexion, abduction, abduction-exorotation, and volume. Groups changed significantly but differently over time in anteflexion, abduction, abduction/exorotation, abduction strength, flexion strength, and volume. Effect sizes varied from 0.19 to 0.00. CONCLUSION: Initial declines in range of motion and strength were followed by recovery, although not always to presurgery levels. Range of motion and volume outcomes were better for SLNB than ALND, but not strength. SLNB surpassed SLNB + CLND in 2 of the range of motion variables. The clinical relevance of these results is negligible.

Personal control after a breast cancer diagnosis: stability and adaptive value.

OBJECTIVE: This longitudinal study aims to gain more insight in both the changes in personal control due to a breast cancer diagnosis, as well as in the stress-buffering effect of personal control. METHODS: Personal control and distress were assessed in breast cancer patients not treated with chemotherapy (n=47), breast cancer patients treated with chemotherapy (n=32) and in healthy women (n=58) at 3, 9 and 15 months after diagnosis. RESULTS: Results indicate that personal control was affected only in patients treated with chemotherapy, particularly right after the completion of treatment. Furthermore, the cross-sectional and longitudinal results provide modest support for the stress-buffering potential of control. CONCLUSIONS: The findings and future directions of research on the role of personal control in the adjustment to cancer will be discussed.

Small size ductal carcinoma in situ of the breast: predictors of positive margins after local excision.

One of the most important predictors of local recurrence after local excision of ductal carcinoma in situ (DCIS) is margin status. The aim was to study the association between margin status and clinical, radiological, and pathological characteristics and to determine predictors of positive margins after local excision of small size (< or = 4 cm) DCIS. Data were tested for differences regarding margin status, and logistic regression was used to determine predictors of margin status. The population consisted of 105 cases. Overall, 51 cases (49%) had free margins and 54 cases (51%) had positive margins. Positive margins were more often associated with a mean mammographic tumor size of 2.1 cm (P = 0.044) and absence of fine granular calcifications (P = 0.004). Also, high-grade (P = 0.013) and a mean pathological size of 3.2 cm (P < 0.001) were associated with positive margins. The only independent predictor of margin status was pathological grade (P = 0.010).

Correlation between imaging and pathology in ductal carcinoma in situ of the breast.

BACKGROUND: It is helpful in planning treatment for patients with ductal carcinoma in situ (DCIS) if the size and grade could be reliably predicted from the mammography. The aims of this study were to determine if the type of calcification can be best used to predict histopathological grade from the mammograms, to examine the association of mammographic appearance of DCIS with grade and to assess the correlation between mammographic size and pathological size. METHODS: Mammographic films and pathological slides of 115 patients treated for DCIS between 1986 and 2000 were reviewed and reclassified by a single radiologist and a single pathologist respectively. Prediction models for the European Pathologist Working Group (EPWG) and Van Nuys classifications were generated by ordinal regression. The association between mammographic appearance and grade was tested with the chi2-test. Relation of mammographic size with pathological size was established using linear regression. The relation was expressed by the correlation coefficient (r). RESULTS: The EPWG classification was correctly predicted in 68%, and the Van Nuys classification in 70% if DCIS was presented as microcalcifications. High grade was associated with presence of linear calcifications (p < 0.001). Association between mammograhic- and pathological size was better for DCIS presented as microcalcifications (r = 0.89, p < 0.001) than for DCIS presented as a density (r = 0.77, p < 0.001). CONCLUSIONS: Prediction of histopathological grade of DCIS presenting as microcalcifications is comparable using the Van Nuys and EPWG classification. There is no strict association of mammographic appearance with histopathological grade. There is a better linear relation between mammographic- and pathological size of DCIS presented as microcalcifications than as a density, although both relations are statistically significant.

Spousal support and changes in distress over time in couples coping with cancer: the role of personal control.

This longitudinal study has examined the associations between perceived supportive and unsupportive spousal behavior and changes in distress in couples coping with cancer. We tested whether people relatively low in their sense of personal control were more responsive to spousal supportive and unsupportive behavior than were people relatively high in personal control. Patients with colorectal cancer and their partners (n = 70) completed questionnaires at two assessment points: 3 (at baseline) and 9 months (at follow-up) after the diagnosis. We assessed perceived spousal supportive (SSL) and unsupportive (SSL-N) behavior, sense of personal control (Pearlin & Schooler's Mastery), and depressive symptoms (CES-D) in both patients and partners. Multilevel analysis (MLwiN) was used to examine changes in distress over time in a dyadic context. Patients and partners who perceived more spousal support reported less distress over time, but this only applied to those relatively low in personal control. Moreover, partners who perceived more unsupportive spousal behavior reported more distress, again only if they were relatively low in personal control. Patients and partners relatively high in personal control reported relatively low levels of distress, regardless of spousal behavior. In conclusion, people relatively low in personal control may be more adversely affected by unsupportive behavior and benefit more from supportive behavior than people relatively high in personal control.

Is self-disclosure in couples coping with cancer associated with improvement in depressive symptoms?

OBJECTIVE: This study examined associations between the degree of self-disclosure and changes in depressive symptoms in couples coping with colorectal cancer. METHOD: Sixty-four newly diagnosed patients and their partners completed a measure of depressive symptoms (Center of Epidemiologic Studies Depression Scale) 3 and 9 months postdiagnosis. Furthermore, approximately 2 months after the first assessment, they engaged in a cancer-related conversation in which the patient was asked to introduce a concern. Each partner's verbalizations of emotions, thoughts, and wishes (i.e., self-disclosures) were coded by independent observers. RESULTS: Patients who reported more depressive symptoms at baseline showed more self-disclosures. Mutual self-disclosure was not associated with lower levels of depressive symptoms in patients and partners as compared with one-sided self-disclosure or low disclosure in both patients and partners. It is important to note that decreases in depressive symptoms over time were least prominent in couples in which the partner disclosed a lot whereas the patient disclosed little. CONCLUSION: These results suggest that mere disclosure of emotions and thoughts to one's intimate partner is not beneficial in reducing distress. Partners' self-disclosure toward patients who disclose few emotions and concerns even appears to be harmful both for patients and partners, given that it reduces the decrease of depressive symptoms over time. If there is a mismatch in the need for self-disclosure within couples, partners with a strong need to talk about their emotions and concerns may be recommended to confide in someone else in their social network or to consult a health care professional.

The value of routine physical examination in the follow up of women with a history of early breast cancer.

PURPOSE: Routine physical examination is recommended in follow up guidelines for women with a history of breast cancer. The objective of this paper is to assess the contribution of routine physical examination in addition to mammography in the early diagnosis of breast cancer recurrences. PATIENTS AND METHODS: The medical follow-up documents of 669 patients were reviewed. 127 contra-lateral breast cancers (CBCs) and 58 loco-regional recurrences (LRRs) in 163 patients were included. The additional contribution of routine physical examination over mammography was evaluated with the proportions of CBCs or LRRs detected by physical examination alone. χ(2) tests were used to compare the difference of contribution of physical examination among subgroups. RESULTS: Seven (6%) out of 127 CBCs and 13 (22%) out of 58 LRRs were detected by routine physical examination alone. Six LRRs (17%; 6/35) were in patients after breast conserving surgery and seven LRRs (30%; 7/23) in patients after mastectomy. There was a trend that the contribution of physical examination is higher in women under 60 years of age in the detection of CBCs (9%; 5/57) and LRRs (28%, 8/29) than in women over 60 years of age (CBCs:3%; 2/70 and LRRs:17%, 5/29; χ(2)=3.090, P=0.079). CONCLUSIONS: Twenty-two percent of loco regional breast cancer recurrences would have been detected later without physical examination. Routine physical examination may be most valuable for women with a history of breast cancer younger than 60 years at follow-up visit.

The adaptive effect of personal control when facing breast cancer: cognitive and behavioural mediators.

This prospective study examines the cognitive and behavioural mediators of the relation between personal control and the initial response to a breast cancer diagnosis as well as subsequent psychological adjustment. A total of 143 patients participated immediately after diagnosis (T1), after surgery (T2) and 2 months after the end of treatment (T3), of whom 92 also completed a questionnaire pre-diagnosis (T0). The buffering effect of personal control on psychological distress shortly after diagnosis was mediated by cancer-specific cognitions, i.e. threat appraisal and coping self-efficacy. Moreover, a strong sense of personal control predicted lower levels of anxiety 2 months after the end of treatment, but was unrelated to distress at T3. The adaptive effect on anxiety was mediated by threat appraisal and active engagement in social life after surgery, but not by active patient participation or coping self-efficacy. These results confirm and explain the adaptive effect of control. Apparently, women with a low sense of control appraise cancer and their personal coping skills more negatively, which makes them vulnerable to distress in response to diagnosis. Furthermore, women with a strong sense of control might regulate anxiety by remaining engaged in social life.

The value of surveillance mammography of the contralateral breast in patients with a history of breast cancer.

PURPOSE: To determine the contribution of surveillance mammography to the early detection of metachronous contralateral breast cancer (MCBC) and to assess its impact on the survival of breast cancer patients with relation to compliance. METHOD: Breast cancer patients (5589) were identified using files from the regional cancer registry of the Comprehensive Cancer Centre North Netherlands (CCCN Groningen, The Netherlands). The programme sensitivity and the impact on prognosis of follow-up mammography with relation to compliance were evaluated in 114 patients who developed MCBC during hospital follow-up. RESULTS: The cumulative MCBC incidence rate at year 10 was 3.4% (95% CI: 2.8-4.0%). The programme sensitivity of surveillance mammography was 59.6% (95% CI: 50.6-68.7). In patients who complied with annual mammography, sensitivity was increased to 70.8% (95% CI: 61.7-80.0). Patients with MCBCs detected by routine mammography have better survival rates than patients with MCBCs detected by other means (HR: 3.18; 95% CI: 1.59-6.34). Though there was a trend towards improved survival in patients being compliant with regular clinical follow-up (HR: 1.69; 95% CI: 0.72-3.96), this was not the case for patients being compliant with annual mammography (HR:1.02; 95% CI:0.50-2.09). CONCLUSION: Mammography is a valuable tool for the early detection of MCBC during hospital follow-up of breast cancer patients and is probably beneficial to survival. The utilisation of follow-up surveillance in breast cancer patients and its potential impact on survival deserve further investigation.

The sentinel node procedure in colon carcinoma: a multi-centre study in The Netherlands.

BACKGROUND: Lymph node status is the most important predictive factor in colorectal carcinoma. Recurrences occur in 20% of the patients without lymph node metastases. The sentinel lymph node (SLN) biopsy is a tool to facilitate identification of micrometastatic disease and aberrant lymphatic drainage. We studied the feasibility of in vivo SLN detection in a multi-centre setting and evaluated nodal micro-staging using immunohistochemistry (IHC). MATERIALS AND METHODS: Sub-serosal injection with Patent Blue dye was used in the SLN procedure in 69 patients operated for localized colon cancer in six Dutch hospitals. Each SLN was examined with routine haematoxylin-eosin staining. In tumour-negative SLNs, we performed CK7/8 or 18 IHC. RESULTS: The procedure was successful in 67 of 69 patients (97%). The SLN was negative in 43 patients. In three cases, it was false negative, resulting in a negative predictive value of 93% and an accuracy of 96%. In 24 of 27 patients with lymph node metastases in a successful SLN procedure, the SLN was positive (sensitivity 89%). In 15 patients, the SLN was the only positive node (21%). In nine patients, we only found micrometastases or isolated tumour cells, resulting in 18% upstaging. Aberrant lymphatic drainage was seen in three patients (4%). CONCLUSION: The SLN procedure in localized colon carcinoma is reliable in a multi-centre setting. It is helpful to identify patients who would be classified as stage II with conventional staging (18%) and who might benefit from adjuvant treatment.

RT-PCR and immunohistochemical evaluation of sentinel lymph nodes after in vivo mapping with Patent Blue V in colon cancer patients.

OBJECTIVE: Lymph node status is the most important predictive factor in the treatment of colorectal cancer. As sentinel lymph node (SLN) biopsy might upstage stage II colon cancer, it could have therapeutic consequences in the future. We investigated the feasibility of in vivo SLN detection with Patent Blue V dye and evaluated nodal microstaging and ultrastaging using cytokeratin immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). MATERIAL AND METHODS: In 30 consecutive patients operated on for colon cancer, subserosal injection with Patent Blue dye was used for SLN detection in four different hospitals under the supervision of one regional coordinator. In searching for occult micrometastases, each SLN was examined at three levels. In tumor-negative SLNs at routine hematoxylin-eosin (H&E) examination (pN0) we performed CK8/CK18 immunohistochemistry (IHC) and RT-PCR for carcinoembryonic antigen (CEA). RESULTS: The procedure was successful in 29 out of 30 patients (97%). The SLN was negative in 18 patients detected by H&E and IHC. In 16 patients the non-SLN was also negative, leading to a negative predictive value of 89% and an accuracy of 93%. Upstaging occurred in 10 patients (33%) - 7 by IHC and 3 by RT-PCR. Aberrant lymphatic drainage was seen in 3 patients (10%). CONCLUSIONS: The SLN concept in colon carcinoma using Patent Blue V is feasible and accurate. It leads to upstaging of nodal status in 33% of patients when IHC and PCR techniques are combined. Therefore, the clinical value of SLN should be the subject of further studies.