Testicular cancer : a longitudinal pilot study on stress response symptoms and quality of life in couples before and after chemotherapy Goals of work The current study was designed to longitudinally examine stress response symptoms -LRB- SRS -RRB- and quality of life -LRB- QoL -RRB- in couples confronted with disseminated testicular cancer . The objectives were to examine couples ' patterns of adjustment over time and possible differences in adjustment between the patient and his partner . Introduction Testicular cancer is a rare disease , although it is the most common tumor in men aged 20 -- 35 years . About 500 new cases are diagnosed each year in The Netherlands -LSB- 1 -RSB- . Testicular cancer is distinguished into seminomas and nonseminomas , and each type accounts for about half of the total . Half of the men with nonseminoma are diagnosed with disseminated disease that is treated with chemotherapy -LSB- 2 -RSB- . Since the introduction of cisplatin-based chemotherapy in the late 1970s , up to 80 % of the patients with disseminated disease can be cured -LSB- 3 -- 5 -RSB- . Chemotherapy for testicular cancer has several acute physical side effects like nausea , fatigue , and neuropathy -LSB- 6 -RSB- . On a psychological level , patients receiving chemotherapy have been found to report anxiety , depression , and distress -LSB- 7 -- 10 -RSB- . The partners of testicular cancer patients receiving chemotherapy may encounter adverse sequelae as well . Partners have to struggle with the fear of potentially losing their significant other . Partners are the primary source of information for family members and friends while their husbands are admitted to the hospital . In addition to this social task , partners often take on the caregiver role between chemotherapy cycles . Caregiving for cancer patients was found to negatively impact a caregiver 's physical and mental health -LSB- 11 -- 13 -RSB- . The impact of testicular cancer on younger couples might differ from the impact on couples who face cancer at an older age . The young couples confronted with testicular cancer might not have been together for a substantial period of time . This can make the relationship more vulnerable to the stressors induced by major life events . Earlier studies have shown that relationships of shorter duration are more sensitive to disruption after a testicular cancer diagnosis -LSB- 14 , 15 -RSB- , although another study did not find such a connection -LSB- 16 -RSB- . Also , couples are confronted with possible treatment-related infertility and sexual difficulties at a time in life where partners are often focused on starting a family . Couples may face several individual and dyadic stressors after the diagnosis of testicular cancer , leading to the experience of distress and lowered quality of life -LRB- QoL -RRB- . This is particularly true when chemotherapy is part of the treatment protocol , as it is a more demanding treatment modality than surgery alone in the case of testicular cancer . Several prospective studies focused on dyadic adjustment and functioning from cancer diagnosis in a variety of sites , up to 1 1/2 years later -LSB- 17 -- 20 -RSB- . Although both patients and partners were reported to suffer from distress , levels of distress did not necessarily correspond within couples . Different patterns of distress and adjustment were found to be associated with gender and health status . Some studies reported that female partners were most vulnerable because they reported higher levels of distress than female and male patients and male partners -LSB- 20 -- 22 -RSB- . One pilot study examined the course of distress and QoL in testicular cancer patients before , during , and after chemotherapy -LRB- complete data on ten patients -RRB- . Patients reported highest levels of distress shortly before the start of chemotherapy . Distress and anxiety decreased over time -LSB- 23 -RSB- . Another recent prospective study on a large group of testicular cancer patients receiving chemotherapy focused on global QoL during the first 2 years after diagnosis . A considerable impairment in global QoL was found after 3 months . However , after 2 years 36 % of patients reported improved functioning compared to baseline -LSB- 24 -RSB- . At the University Medical Center Groningen -LRB- UMCG -RRB- in The Netherlands , a tertiairy referral center for patients with testicular cancer , and at the University of Texas M. D. Anderson Cancer Center , USA considerable institutional research was done into epidemiology , short - and long-term medical , and sexual outcomes of testicular cancer -LSB- 25 -- 28 -RSB- . These cross-sectional and retrospective studies were done on QoL of testicular survivors -LSB- 29 -RSB- , their partners -LSB- 30 -RSB- , and marital and sexual satisfaction -LSB- 16 , 31 -- 33 -RSB- . We chose to expand these findings by performing a prospective study , and the findings of Trask and Fossa by including partners in our prospective study . Patterns of stress response symptoms -LRB- SRS -RRB- and QoL of patients and partners were examined at three time points during the first year . SRS can occur after a range of traumatic events , including cancer . They involve intrusive thoughts and avoidance of thoughts and situations that remind them of the event , and are often studied in cancer patients -LSB- 34 -RSB- . Goals of the present study were : -LRB- 1 -RRB- to explore differences and relationships between patients and partners ' SRS and QoL and to relate those to relationship aspects -LRB- duration and presence of children -RRB- ; -LRB- 2 -RRB- to examine change over time in SRS and QoL in patients and partners ; -LRB- 3 -RRB- to relate earlier levels of SRS and QoL in patients and partners to later levels ; and -LRB- 4 -RRB- to examine differences in QoL of patients and partners with that of a reference group of men and women . Materials and methods Procedure and participants All patients diagnosed with a disseminated nonseminomatous testicular tumor who consecutively visited the UMCG in The Netherlands for treatment between April 2001 and March 2004 and who were married or cohabiting were approached for this study . Only patients who received chemotherapy and had a steady relationship -LRB- n = 30 -RRB- could be included in this study . Other inclusion criteria were age over 18 years at study entry , sufficient command of the Dutch language , no previous treatment for cancer , and absence of a psychiatric history . The study was introduced to the patients and their partners after orchiectomy -LRB- removal of the affected testicle -RRB- was performed . Couples received a questionnaire at the following three time points : after orchiectomy but before the start of chemotherapy -LRB- T1 -RRB- , immediately after completion of chemotherapy , which is approximately 3 months after T1 -LRB- T2 -RRB- , and 1 year after T1 -LRB- T3 -RRB- . The patients received four cycles of cisplatin , etoposide , and bleomycin with a 3-week interval between each cycle . Couples received a letter with information about the objectives of the study , an informed consent form , the questionnaires , and a prepaid return envelope . Thirty of the 70 patients diagnosed during the above-mentioned time period appeared to meet all of the inclusion criteria . They and their partners were approached to participate in the study . Of the eligible 30 couples , 21 participated -LRB- 70 % -RRB- . Two couples did not complete all three measurement times , therefore , only 19 couples provided complete data . The study was approved by the Medical Ethics Committee of the UMCG . Measurements Sociodemographics : Data on the following sociodemographic variables were collected at T1 : age , educational level , employment status , presence of children , and duration of the relationship . Highest educational level completed was measured on a seven-point scale : primary school -LSB- 1 -RSB- , and lower vocational -LSB- 2 -RSB- , lower secondary -LSB- 3 -RSB- , middle secondary -LSB- 4 -RSB- , high secondary -LSB- 5 -RSB- , higher vocational degrees -LSB- 6 -RSB- , and advanced university -LSB- 7 -RSB- . Employment status could be indicated as employed for wages , housekeeping , student , unemployed , unable to work , or retired . SRS were measured with the Impact of Event Scale -LRB- IES -RRB- -LSB- 35 , 36 -RSB- . This scale -LRB- 15 items -RRB- makes an inventory of the extent to which a subject is currently occupied with an event by measuring intrusion -LRB- intrusively experienced ideas , images , feelings , or bad dreams about the event ; 7 items -RRB- and avoidance of unpleasant feelings or memories of the event -LRB- 8 items -RRB- , resulting in a total score of SRS . Patients and partners rated the frequency of SRS with respect to his cancer during the preceding 7 days . Examples of items include : `` Any reminder brings back feelings about it '' -LRB- intrusion -RRB- and `` I try to banish it from my memory . '' The IES is a valid instrument for measuring cancer-related SRS -LSB- 37 , 38 -RSB- . With this questionnaire , information was obtained about the degree to which confrontation with testicular cancer was influencing the current daily life of the respondent . Higher scores indicate more SRS . The Dutch version of the IES indicates a total score of more than 26 as severe SRS , for which psychological help is recommended . Reliability of this scale was good for patients -LRB- Cronbach 's alpha for the different measurement times ranged from 0.82 to 0.89 -RRB- and for partners -LRB- Cronbach 's alpha for the different measurement times ranged from 0.78 to 0.93 -RRB- . QoL was measured with three subscales of the RAND-36 -LSB- 39 -RSB- : physical functioning -LRB- ten items -RRB- , social functioning -LRB- two items -RRB- and mental health -LRB- five items -RRB- . To avoid statistical problems due to multiple comparisons , we chose these three subscales as a representation of overall QoL . The RAND-36 measures generic QoL . After recoding and transformation , scores on the subscales could range from 0 to 100 . Higher scores indicate a better QoL . Reliability of these scales was good to very good for patients -LRB- Cronbach 's alpha for the different measurement times ranged from 0.67 to 0.90 -RRB- and for partners -LRB- Cronbach 's alpha for the different measurement times ranged from 0.75 to 0.92 -RRB- . The Dutch manual for the RAND-36 provides reference scores . These comprised the mean scores of a group of 691 nonselected men and 372 nonselected women from a random representative sample of persons aged 18 years and older from the population register of a municipality in the north of The Netherlands -LRB- number of inhabitants = 108,000 -RRB- . The mean age of the persons in the total random sample was 44.1 years -LRB- range 18 -- 89 years -RRB- -LSB- 39 -RSB- . Statistical analyses The database consisted of matched pairs of patients and partners , making analyses on pair level possible . Paired t tests and chi-square test were performed to examine differences in sociodemographics between patients and partners . Wilcoxon signed rank test -LRB- because of small sample size -RRB- and correlations were computed to examine differences and relationships in SRS and QoL between patients and partners . Independent t tests were performed for having children -LRB- yes or no -RRB- with SRS and QoL . Pearson 's product moment correlations were calculated to examine the relationship between duration of the relationship and patients and partners ' SRS and QoL . Repeated measures analysis of variance -LRB- ANOVA -RRB- was used to examine change over time in functioning . Pearson 's product moment correlations were calculated to examine relationships between the functioning of patient and that of the partner and between measurement times . Strong correlation coefficients -LRB- > 0.50 -RRB- indicate consistency between measurement times and stable responses between earlier and later levels of functioning . Independent t tests were performed to compare QoL of patients and partners with those of a reference group of men and women . Results Sociodemographic and treatment-related variables Sociodemographic and treatment related variables are reported in Table 1 . Patients were older than partners -LRB- t = − 3.1 , p < 0.01 -RRB- . The mean time couples had been together was 5.7 years . Eighteen patients were employed for wages and 1 was a student , whereas 11 partners were employed for wages , 4 were home-keepers and the remaining 4 partners were students -LRB- chi-square = 19.0 , p = 0.04 -RRB- . Of the 21 couples , 5 had children and 14 did not . After chemotherapy was completed -LRB- at T2 -RRB- , all patients were restaged . Patients without biochemical or radiological abnormalities were considered to have reached complete remission -LRB- n = 8 -RRB- . In case of proven residual disease , a resection of residual retroperitoneal tumor mass -LRB- RRRTM -RRB- was performed . Eleven patients underwent this surgery and were considered to be in complete remission afterward . None of the 19 patients experienced a relapse during follow-up -LRB- up to T3 -RRB- . Table 1Descriptives of sociodemographic and treatment-related variables PatientPartnerMeanSDMeanSDAge -LRB- years -RRB- b31 .66.628.97.6 Range19 .9 -- 43.519.8 -- 44.7 Duration relationship -LRB- years -RRB- 5.76.3 Range1 -- 22Education level3 .61.44.01.6 N % N % Employment statusb Employed for wages18951158 Student15421 Housewife421Children Yes526 No1474RRRTM + Yes1158 No842RRRTM Resection of residual retroperitoneal tumor massap < 0.01 bp < 0.05 Patients ' and partners ' SRS and QoL At T1 , SRS of patients were moderately strongly and negatively related to those of partners -LRB- r = − 0.48 , p < 0.05 -RRB- . At T2 , social functioning of patients was moderately strongly and positively related to that of partners -LRB- r = 0.53 , p < 0.05 -RRB- . At the three measurement times all other correlations between patients ' SRS and QoL and those of partners were low to moderate , ranging from r = 0.04 to 0.34 , and not statistically significant . At T1 , in two couples , both patient and partner experienced SRS above the cut-off point . At T2 and T3 there were no couples in which both patient and partner experienced SRS above the cut-off point . Wilcoxon tests showed only one significant difference between patients and partners ' functioning . At T2 , patients reported a lower level of physical functioning than did partners -LRB- Z = − 2.6 , p < 0.01 -RRB- . Independent t tests did not show a significant relationship between having children and SRS for patients at all measurement times , and for partners at T1 and T2 . At T3 partners with children reported higher levels of SRS than partners who did not have children -LRB- t = 2.6 , p = 0.018 -RRB- . The presence of children was unrelated to patients ' and partners ' QoL at all measurement times . The duration of the relationship was not significantly related to the patients ' or partner 's SRS or QoL at all measurement times and relationships were absent to very weak . The course of SRS and QoL over time in patients and partners Repeated measures ANOVA showed that the SRS of patients fluctuated according to a quadratic trend : The highest level was reported at T1 and after a decrease at T2 , the level was increased again somewhat at T3 . Earlier levels of SRS in patients were highly positively related to later levels -LRB- Table 2 -RRB- . At T1 , five of the patients -LRB- 26 % -RRB- reported stress response levels above the cut-off point ; at T2 , two patients -LRB- 11 % -RRB- ; and at T3 , three patients -LRB- 16 % -RRB- . Two patients reported clinically elevated levels of stress response levels at all measurement times . For partners the level of SRS declined , via a linear trend . Partners ' reports of stress response levels were moderately strongly related between T1 and T2 , strongly between T2 and T3 , and the relationship between T1 and T3 was weak -LRB- Table 2 -RRB- . At T1 , ten of the partners -LRB- 53 % -RRB- reported stress response levels above the cut-off point , at T2 , six -LRB- 32 % -RRB- , and at T3 , two -LRB- 10.5 % -RRB- . One partner reported clinically elevated levels of stress response levels at all measurement times . Table 2SRS and QoL of patients and partners T1T2T3Reference groupRepeated measures ANOVAT1 -- T2T2 -- T3T1 -- T3Mean -LRB- SD -RRB- Mean -LRB- SD -RRB- Mean -LRB- SD -RRB- Mean -LRB- SD -RRB- FprprprpStress response symptomsPatient18 .1 -LRB- 13.0 -RRB- 10.2 -LRB- 10.7 -RRB- 12.3 -LRB- 9.9 -RRB- 7.90.0120.650.0020.710.0010.700.001 Partner25 .8 -LRB- 9.3 -RRB- 15.2 -LRB- 12.6 -RRB- 12.1 -LRB- 12.4 -RRB- 17.70.0010.41 ns0 .640.0030.16 nsPhysical functioningPatient93 .4 -LRB- 10.8 -RRB- 70.5 -LRB- 23.4 -RRB- 92.6 -LRB- 13.3 -RRB- 84.5 -LRB- 22.3 -RRB- a , b , c21 .40.0010.28 ns0 .38 ns0 .20 nsPartner90 .2 -LRB- 19.0 -RRB- 90.8 -LRB- 19.0 -RRB- 89.7 -LRB- 19.9 -RRB- 80.7 -LRB- 23.6 -RRB- b , d0 .19 ns0 .790.0010.800.0010.970.001 Social functioningPatient77 .6 -LRB- 19.7 -RRB- 71.1 -LRB- 22.8 -RRB- 90.8 -LRB- 13.1 -RRB- 88.4 -LRB- 19.6 -RRB- d , e9 .00.0080.610.0090.19 ns0 .17 nsPartner72 .1 -LRB- 20.2 -RRB- 77.6 -LRB- 20.7 -RRB- f84 .5 -LRB- 16.5 -RRB- 86.1 -LRB- 20.9 -RRB- a12 .90.0020.600.0070.37 ns0 .680.001 Mental healthPatient68 .2 -LRB- 22.3 -RRB- 77.5 -LRB- 11.9 -RRB- 81.9 -LRB- 13.4 -RRB- 79.4 -LRB- 17.3 -RRB- d6 .70.0190.550.0170.33 ns0 .23 nsPartner69 .1 -LRB- 13.6 -RRB- 71.2 -LRB- 15.6 -RRB- 74.3 -LRB- 15.1 -RRB- 75.5 -LRB- 18.9 -RRB- 2.6 ns0 .720.0010.640.0040.520.023 ap < 0.01 -LRB- independent t test T1 and reference group -RRB- bp < 0.05 -LRB- independent t test T2 and reference group -RRB- cp < 0.05 -LRB- independent t test T3 and reference group -RRB- dp < 0.05 -LRB- independent t test T1 and reference group -RRB- ep < 0.01 -LRB- independent t test T2 and reference group -RRB- fp < 0.01 -LRB- Wilcoxon test patients and spouses -RRB- Lower physical functioning was reported by patients at T2 compared to T1 , but physical functioning returned to baseline level at T3 . Earlier levels of physical functioning in patients were not significantly related to later levels , and correlations were low . A decline in social functioning of patients was also found at T2 compared to T1 , but higher social functioning than at baseline was found at T3 . Social functioning of patients at T1 was positively and strongly related to functioning at T2 , but the relationships between T2 -- T3 and T1 -- T3 were low to moderate . Mental health of patients improved over time . Mental health at T1 was positively and strongly related to levels at T2 , and weakly to levels at T3 . The relationship between mental health at T2 and T3 was moderately strong . For partners , no significant time effects were found for physical functioning and mental health . Earlier levels of physical functioning and mental health of partners were highly and positively related to later levels . Social functioning of partners improved over the year and was highly positively related between T1 and T2 and between T1 and T3 . The relationship between T2 and T3 was moderately strong . -LRB- Table 2 -RRB- . QoL of patients and partners compared to that of a reference group of men and women At T1 , patients -LRB- t = − 3.4 , p < 0.01 -RRB- and partners -LRB- t = − 2.1 , p < 0.05 -RRB- reported better physical functioning than the reference groups . Patients -LRB- t = 2.3 , p < 0.05 -RRB- and partners -LRB- t = 2.9 , p < 0.01 -RRB- reported worse social functioning than the reference groups at T1 , and patients -LRB- t = 2.2 , p < 0.05 -RRB- reported worse mental health at T1 . At T2 , patients reported worse physical functioning than the reference group of men -LRB- t = 2.6 , p < 0.02 -RRB- but partners reported better physical functioning than the reference group of women -LRB- t = − 2.2 , p < 0.05 -RRB- . Patients also reported worse social functioning than the reference men at T2 -LRB- t = 3.3 , p < 0.01 -RRB- . No differences were found between the patients ' and partners ' mental health and the norm groups at T2 . Only one significant difference was found at T3 : Patients reported better physical functioning than men in the reference group -LRB- t = − 2.6 , p < 0.02 -RRB- -LRB- Table 2 -RRB- . Discussion The present study was the first to prospectively and longitudinally examine psychosocial functioning in both testicular cancer patients and their partners . We focused on SRS and QoL -LRB- physical functioning , social functioning , and mental health -RRB- after orchiectomy but before the start of chemotherapy , immediately after completion of chemotherapy , and 9 months later -LRB- 1 year follow-up -RRB- . SRS in couples were most salient before the start of chemotherapy . Twenty-six percent of patients reported clinically elevated SRS at this time , a number comparable to the 30 % of patients with clinically elevated distress found in a recent study on testicular cancer patients -LSB- 23 -RSB- . A review of stress response syndromes in adult cancer populations showed that the incidence of clinically elevated SRS ranged from 3 to 4 % in patients recently diagnosed with early stage cancer -LSB- 34 -RSB- . The majority of these studies used the same questionnaire for measuring SRS as we did . The same review identified younger age , greater proximity to diagnosis , more advanced disease , and greater treatment intensity as risk factors for a higher level of SRS . The much higher percentage found in our study at the first measurement time may be explained by the prevalence of these four risk factors in our patient group . Not only did patients appear distressed , but also almost twice as many of the partners compared to patients reported clinically elevated levels of SRS . Female sex was found to correlate with greater stress response symptomatology in cancer populations -LSB- 34 -RSB- . Of course , these spouses are not patients themselves , but they obviously face cancer-related fears and worries as well . Our results affirm earlier findings that female spouses of cancer patients are vulnerable to distress , and often report higher levels of distress compared to their male counterparts -LSB- 20 , 21 , 40 -- 42 -RSB- . It was also found that partners who had children experienced more SRS a year after diagnosis compared to partners without children . This higher level of distress might also be a result of caregiving tasks that are often the domain of female partners . SRS in couples decreased after completion of chemotherapy . One year after diagnosis , stress response levels in patients rose slightly , but they continued to decrease in partners . These patterns suggest that the period before chemotherapy commences is most stressful , and that recovery seems to occur within a year . At the time of the first measurement the responses of the couples seem to be colored by the fact that they had recently learned the diagnosis , and the outcome of treatment remained uncertain . Concerns of couples about side effects of chemotherapy such as nausea , the possibility of immunodeficiency , and hair loss may contribute to distress . Partners also have caregiving tasks that can exacerbate their distress -LSB- 22 -RSB- . All couples in this study received positive news about the results of treatment , and 1 year after diagnosis none of the patients had experienced a relapse of disease . Couples seemed to have recovered from this major life event over the year , possibly as a consequence of the success of treatment reducing insecurity about outcome . An interesting finding was that before commencement of chemotherapy , the level of SRS of patient and partner was inversely related . When one spouse was reporting more SRS , the other reported less . This might be a psychological mechanism through which spouses want to protect one another from their own distress , a finding reported before in studies on couples facing cancer -LSB- 40 -RSB- . Another possible interpretation might be that patients who expressed very low levels of distress were using denial , avoidance , or other repressive psychological mechanisms while their partners carried the psychological burden of stress . A patient who expresses high distress may also allow his spouse to assume a stronger supportive role , and thus reduce her expression of stress . In line with the medical trajectory , physical functioning of patients was worst after completion of chemotherapy . As a consequence of chemotherapy , many patients still experience adverse side effects , including fatigue and a sense of physical exhaustion . It is surprising to note that physical functioning of patients was better than that of the reference group before start of chemotherapy and 1 year later . The first measurement occurred shortly after removal of the affected testicle , and patients may have experienced physical relief after the initiation of treatment . It may also be that age contributed to the difference found between the patient group and the reference group . Younger age is associated with better physical functioning -LSB- 39 -RSB- , and the mean age of the patients in this study was somewhat more than 10 years lower than that of the reference group . There may have been other differences from the reference group as well , such as physical activity and SES . Partners ' physical functioning did not change over the year but they also experienced better physical functioning than the reference group before and after chemotherapy . In an earlier cross-sectional study we found that partners of men who survived testicular cancer between 1 -- 20 years reported better physical functioning than a reference group of women , even years after diagnosis -LSB- 30 -RSB- . Partners of testicular cancer patients may have changed the evaluation of their own health in a positive way after witnessing the diagnosis and treatment of a life-threatening illness . In patients , social functioning was worst immediately after completion of chemotherapy , and in spouses before start of chemotherapy . Before start of chemotherapy , both partners reported worse social functioning compared to the reference groups . Before chemotherapy starts , couples are probably overwhelmed by the implications of a cancer diagnosis and focus more on the treatment to come rather than on being socially active as usual . As a consequence of chemotherapy , patients may still suffer from negative side effects like fatigue and impaired physical functioning , which in turn may affect their social functioning . Social functioning in patients and partners was positively related after completion of chemotherapy , meaning that when one partner experienced better social functioning the other also did . Couples had comparable social functioning to that of the reference groups 1 year after diagnosis ; they seem to have returned to their usual social activities . This finding is in line with studies on testicular cancer survivors that show little or no change in social contacts and work activities -LSB- 6 , 43 -RSB- . Mental health of patients improved over the year . It was poorer than that of men in the reference group but only before start of chemotherapy . Mental health of partners was comparable throughout the year and to that of a reference group of women , despite the high level of SRS they reported before start of chemotherapy . SRS apparently are a different expression of mental functioning and may be encapsulated or separated out . It appeared that functioning in couples facing testicular cancer was not similar in patients and partners . Testicular cancer patients showed u-shaped trajectories of SRS , physical functioning , and social functioning . This pattern seemingly followed the medical trajectory they had undergone and was found before in a large group of testicular cancer patients -LSB- 24 -RSB- . Mental health of patients improved over the year . Spouses reported a decline in SRS and an improvement in social functioning , but no change in physical functioning or mental health over the year . Differences between patients and partners were also noticeable in stability of functioning . In patients , earlier levels of SRS were strongly predictive of later levels while less individual stability was found with regard to physical and social functioning and to mental health . Partners reported less individual stability in SRS over time , although individual stability was found between T2 and T3 . However , partners were individually highly consistent in their reports of physical functioning and somewhat less strong in mental health and social functioning . In addition , correlations between the functioning of patients and partners were moderate to very low . We also found that at the second and third measurement time , there were no couples in which both the patient and the partner reported clinically elevated levels of SRS . This finding confirms the lack of correspondence in functioning between patient and partner . These findings support recent studies that found different adjustment patterns for patients and partners , and a lack of correspondence in functioning -LSB- 19 , 20 -RSB- . Research is needed to examine if these different reaction patterns to a cancer diagnosis affect the marital relationship . This study has some limitations . First , the possibility of including couples was limited because testicular cancer has a low incidence , and because of the young age of patients at diagnosis , part of this group will not yet have established a steady relationship . Second , no information was available on the functioning of couples who declined to participate . They may have been those who were functioning best or worst , thus biasing the results in either direction . Third , because of the limited sample size , variables that measure more in depth relationship aspects like marital satisfaction were not included in this study . In a previous retrospective study on testicular cancer , factors identified as important for couple adjustment like good communication , spousal support , and marital satisfaction all appeared to facilitate better functioning -LSB- 32 -RSB- . These moderating factors in adjustment of both patient and spouse deserve to be studied prospectively in the future . In summary , this study was the first longitudinal prospective exploration of functioning in couples facing testicular cancer during the first year after the diagnosis . Patients confronted with disseminated testicular cancer and their partners reacted differently to this stressor . Clinically elevated stress response levels were present in one third of patients and half of the partners before start of chemotherapy . Patients reported worst mental health before start of chemotherapy , and worst physical and social functioning immediately after completion of chemotherapy . Partners reported an improvement in social functioning , and no change in physical functioning and mental health over the year . QoL of patients and partners was comparable to that of the reference groups a year after start of chemotherapy , patients even reported better physical functioning at that time . These findings support earlier retrospective studies in testicular cancer survivors and their spouses that also reported few long-term effects in psychosocial functioning in the group overall , but that identified a small group that remains distressed -LSB- 16 , 31 , 32 -RSB- . Little correspondence was found in the functioning of the partners . Findings should be regarded as preliminary , as the study sample was limited in size . However , clinicians can be reassured that the effect of disseminated testicular cancer on the QoL of patients and their partners seems to be temporary , although a minority does seem to need clinical attention for SRS .

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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O B O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O 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Pancreatic intraductal papillary-mucinous neoplasms : a new and evolving entity For a long time , intraductal tumors of the pancreas were neglected because they were misdiagnosed as mucinous cystadenocarcinoma , ordinary ductal adenocarcinoma , or chronic pancreatitis . Only in recent years have they been recognized as clinical and pathological entities . Most common are the intraductal papillary-mucinous neoplasms . Although they show an adenoma-carcinoma sequence , they have proved to have a more favorable prognosis than ductal adenocarcinoma , when resected in a preinvasive state . Recently , it has become clear that they constitute a heterogeneous group with at least four subtypes . Their stratification reveals that the various intraductal papillary-mucinous neoplasm subtypes have different biological properties with different prognostic implications . Historical notes and a rising incidence The pancreatic tumors that are characterized by an intraductal origin and growth pattern include intraductal papillary-mucinous neoplasms -LSB- 3 , 24 , 41 -RSB- , intraductal tubular carcinomas -LSB- 22 , 45 -RSB- , intraductal tubular adenomas of the pyloric type -LSB- 6 -RSB- , and intraductal acinar cell carcinomas -LSB- 15 -RSB- . Most common are the intraductal papillary-mucinous neoplasms -LRB- IPMNs -RRB- . They are mucin-producing epithelial tumors that usually show a papillary architecture and are associated with dilatation of the ducts . Before 1990 , these tumors were thought to be rare . They first started to be recognized approximately 20 years ago -LSB- 31 , 36 , 39 -RSB- , when the many different names given to the tumor in the 1980s were replaced by the term IPMN -LSB- 41 -RSB- . This name was also introduced in the classification of exocrine pancreatic tumors propagated by the World Health Organization -LRB- WHO -RRB- -LSB- 24 -RSB- and the fascicles of the Armed Forces Institute of Pathology -LSB- 44 -RSB- . Since then , IPMNs have been reported with increasing frequency -LRB- Table 1 -RRB- and currently account for about 7 % of clinically diagnosed pancreatic neoplasms and up to 16 % of surgically resected pancreatic neoplasms and for almost 50 % of pancreatic cysts found incidentally -LSB- 8 , 17 -RSB- . When only the cystic tumors of the pancreas are considered , IPMNs take first place , with a frequency of 24 % -LSB- 26 -RSB- . Table 1Incidence data on intraductal papillary-mucinous neoplasmsAuthorPeriod 1Number of incidencePeriod 2Number of incidenceSohn et al. -LSB- 43 -RSB- 1987 -- 2001582001 -- 200378Wada et al. -LSB- 47 -RSB- 1988 -- 2000632001 -- 200337Our series1981 -- 2000552001 -- 200750 The new incidence data on IPMNs raise the question whether their increase in number is real or not . Of course , it is difficult to accept that IPMNs might have been overlooked in the past , not only clinically but also morphologically . There are good reasons , however , to believe that IPMNs did always exist and did not really increase in frequency . One reason is related to the rapid improvements in modern imaging techniques , which enable more precise recognition of cystic lesions , even if they are small and asymptomatic . Another is connected with the decreasing risk of pancreatic surgery . The most important fact , however , may be that until 1999 , the distinction between IPMNs and mucinous cystic neoplasms -LRB- MCNs -RRB- was unclear , so that many IPMNs were classified as MCNs -LSB- 50 -RSB- or regarded as ductal adenocarcinomas or chronic pancreatitis . Adenoma-carcinoma sequence In IPMNs , the normal ductal epithelium is replaced by mucin-producing columnar cells showing papillary proliferations and variable degrees of cellular atypia , even within an individual neoplasm . They are graded according to the most atypical area as IPMN with low grade dysplasia -LRB- adenoma -RRB- , IPMN with moderate dysplasia -LRB- borderline -RRB- , and IPMN with high grade dysplasia -LRB- carcinoma in situ -RRB- . An invasive component may be found in 38 -- 50 % of the cases -LSB- 7 , 26 , 40 , 43 -RSB- . Progression from adenoma to carcinoma is estimated to occur at about 5 years -LSB- 43 -RSB- . IPMNs therefore provide a model of neoplastic progression from a benign intraductal neoplasm through increasing grades of dysplasia to invasive carcinoma . Prognosis after resection Between 80 and 90 % of IPMNs are surgically resectable . For these IPMNs , a 5-year survival rate of 77 -- 100 % was reported , provided the tumors did not have an invasive component -LRB- Table 2 -RRB- . By contrast , IPMNs with an invasive component had a 3 - to 5-year survival rate of only 36 -- 46 % -LSB- 12 , 16 , 43 -RSB- -LRB- Table 2 -RRB- . Interestingly , the survival rate did not appear to be dependent on the grade of dysplasia in the IPMN if there was no invasive component -LSB- 12 , 16 , 43 , 47 -RSB- . These data imply that the overall outcome of IPMNs therefore largely depends on the presence of an invasive component . If the tumor is already invasive , criteria for a poor outcome are lymph node involvement , vascular invasion , and bilirubin elevation -LSB- 13 -RSB- . A comparison of the prognosis of all patients with invasive IPMNs with that of patients with ductal adenocarcinoma reveals that patients with IPMNs survive longer than those with ductal adenocarcinomas -LSB- 29 , 40 , 43 -RSB- . Table 2Five year survival rate and recurrence in 349a intraductal papillary-mucinous neoplasms NoninvasiveInvasive77 -- 100 % 36 -- 46 % No recurrence93 -- 98.7 % 52 -- 70 % Recurrence1 .3 -- 7 % 30 -- 48 % Localup to 6 % 8 -- 48 % Distant -LRB- metastases -RRB- 1 % 12 % Both0 % 10 -- 48 % a -LSB- 12 , 43 , 47 -RSB- Several studies have reported recurrences after resection of noninvasive IPMNs , some of which revealed only moderate dysplasia -LSB- 12 , 43 , 47 , 48 -RSB- . The recurrences were either local or metastatic -LRB- Table 2 -RRB- . To explain the recurrences , particularly the local ones , it has to be assumed that either tumor tissue was overlooked at the pancreatic resection margin , or an invasive component remained undetected in the resected specimen , or there was multifocal disease . The last possibility has to be considered if the surgical margins were negative and the recurrence occurred in the pancreatic remnant . This has been observed only in a few cases -LSB- 40 -RSB- . When metastatic recurrences occur , it is most likely that they resulted from inadequate sampling that failed to detect an invasive component . Regarding the impact of a positive resection margin on IPMN recurrence , it is interesting to note that it has been reported that even IPMNs with positive margins did not recur during a median follow-up period varying from 19 -- 40 months -LSB- 13 , 48 -RSB- . The reason for this phenomenon might be that the growth of the remaining intraductal tumor tissue is so slow that clinical symptoms only appear after a follow-up period of 2 to 3 years . However , even if intraductal recurrences may take a long time to become clinically apparent , a positive margin in any IPMN case should lead to further tissue resection . Histological type and prognosis In 1991 , it was reported that the invasive component of IPMNs corresponded either to an ordinary ductal adenocarcinoma or , more frequently , to that of a mucinous -LRB- colloid -RRB- carcinoma -LSB- 49 -RSB- . This observation suggested that IPMNs form a group of heterogeneous neoplasms . A further argument for the heterogeneity of IPMNs was the detection of IPMNs in branch ducts rather than in the main duct , where most of the IPMNs are found . Finally , it was recognized that IPMNs differ in their histological and cytological features and in their mucin profile -LSB- 3 , 4 , 18 , 28 , 32 , 33 -RSB- . Currently , four subtypes of IPMN can be distinguished : an intestinal type , a pancreatobiliary type , an oncocytic type , and a gastric type -LSB- 18 -RSB- . The most common type of IPMN is the intestinal type -LRB- Table 3 -RRB- . It usually occurs in the main duct of the pancreatic head -LSB- 9 -RSB- and shows a villous growth pattern similar to that of villous adenoma in the colon . It also expresses MUC2 and CDX2 but not MUC1 -LRB- Fig. 1a , b -RRB- . When this IPMN type becomes invasive , the invasive component resembles mucinous -LRB- colloid -RRB- carcinoma -LSB- 5 , 28 -RSB- , a tumor of which at least 80 % is composed of pools of extracellular mucin containing single cells or strands of neoplastic glandular epithelium or even a small component of signet ring cells . Patients with colloid carcinoma have a 55 % 5-year survival rate after resection -LSB- 5 -RSB- . These tumors therefore seem to be much less aggressive than ordinary ductal adenocarcinomas . Fig. 1Histological subtypes of intraductal papillary-mucinous neoplasms of the pancreas and their usual mucin pattern . a , b IPMN of the intestinal type positive for MUC2 ; c , d IPMN of the pancreatobiliary type positive for MUC1 ; e , f IPMN of the oncocytic type showing scattered positivity for MUC2 ; g , h IPMN of the gastric type , positive for MUC5Table 3Histopathological data on 105 intraductal papillary-mucinous neoplasms collected during a period of 26 yearsIPMNGastric -LRB- n = 27 -RRB- -LRB- 26 % -RRB- Intestinal -LRB- n = 57 -RRB- -LRB- 54 % -RRB- Pancreatobiliary -LRB- n = 7 -RRB- -LRB- 7 % -RRB- Oncocytic -LRB- n = 14 -RRB- -LRB- 13 % -RRB- Noninvasive -LRB- 65 % -RRB- n = 20 -LRB- 74 % -RRB- n = 35 -LRB- 62 % -RRB- n = 3 -LRB- 43 % -RRB- n = 10 -LRB- 72 % -RRB- Adenoma91215Borderline71821Carcinoma in situ4504Invasive -LRB- 35 % -RRB- n = 7 -LRB- 26 % -RRB- n = 22 -LRB- 38 % -RRB- n = 4 -LRB- 57 % -RRB- n = 4 -LRB- 28 % -RRB- The pancreatobiliary type of IPMN is much rarer than the intestinal type IPMN -LRB- Table 3 -RRB- . It shows complex arborizing papillae and expresses MUC1 only -LRB- Fig. 1c , d -RRB- . Its invasive component usually corresponds to a conventional ductal adenocarcinoma . The prognosis of this type of IPMN , if invasive , seems to be similar to that of ductal adenocarcinoma and therefore poorer than that of the intestinal type of IPMN -LSB- 4 -RSB- . The oncocytic type of IPMN -LRB- also called intraductal oncocytic papillary neoplasm -LSB- 2 -RSB- -RRB- shows the same complex papillae as the pancreatobiliary type , but the lining cells reveal strongly eosinophilic cytoplasm . In addition , there are often numerous goblet cells . The tumor cells express MUC1 and MUC2 inconsistently -LRB- Fig. 1e , f -RRB- . With fewer than 20 cases reported in the literature to date -LSB- 2 , 20 , 34 , 35 , 37 , 38 , 42 -RSB- , the clinical and pathological behavior of this type is still unclear . Most of the cases -LRB- 94 % -RRB- were diagnosed as carcinoma , some of them with an invasive component or even distant metastases -LSB- 37 -RSB- . As the follow-up in this patient group is very short , no relevant data are available yet on survival and outcome . The gastric type of IPMN exhibits papillary projections lined by epithelial cells resembling gastric foveolar cells and shows pyloric gland-like structures at the base of the papillae . These cells express MUC5 -LRB- Fig. 1g , h -RRB- , while MUC1 , MUC2 , or CDX2 positivity is only occasionally observed . The gastric type of IPMN corresponds to the branch duct type , which occurs in the periphery of the pancreatic parenchyma , most often in the uncinate process , where it usually presents as a multicystic lesion with cysts no larger than 3 cm -LSB- 9 -RSB- . The gastric type seems to be less aggressive , i.e. , less invasive , than the other IPMN subtypes -LSB- 10 , 25 , 33 , 46 -RSB- but may show severe cellular atypia in a few cases -LRB- up to 25 % -RRB- -LSB- 46 -RSB- -LRB- Table 3 , Fig. 2 -RRB- The size of the lesion was unrelated to the grade of cellular atypia -LSB- 46 -RSB- . Fig. 2IPMN of the gastric type showing severe cellular atypia and MUC5 positivity Interestingly , pancreatic intraepithelial neoplasia -LRB- PanIN -RRB- - like complexes are frequently observed next to gastric type IPMNs . This raises the question whether IPMNs of the gastric type are a focal accentuation of a diffuse disease rather than a localized lesion . They might therefore also be related to the small peripheral cystic changes described by Kimura et al. -LSB- 21 -RSB- in non-neoplastic pancreata or the patchy lobular fibrosis associated with PanIN-1B lesions described by Detlefsen et al. -LSB- 14 -RSB- -LRB- Fig. 3 -RRB- . If this were the case , IPMNs of the gastric type would actually be large PanIN-1 lesions . An argument for this assumption is that both IPMNs of the gastric type and PanIN-1 lesions stain for MUC5 in the absence of MUC1 and MUC2 positivity . This assumption would also explain why it is difficult to distinguish PanIN lesions from some IPMNs -LSB- 27 -RSB- -LRB- Fig. 4 -RRB- , despite a consensus definition of both lesions -LSB- 19 -RSB- . Fig. 3PanIN-1 lesion associated with lobular fibrosisFig . 4Small multicystic duct-associated lesion in the periphery of pancreatic tissue suggestive of an IPMN of the gastric type but difficult to distinguish from a large PanIN-1 lesion Although the malignant potential of IPMNs of the gastric type seems to be rather low , it has to be pointed out that the fibrocystic changes that have been described in pancreata removed from patients with a strong family history of pancreatic cancer -LSB- 11 , 30 -RSB- are similar , if not identical , to IPMNs of the gastric type and their associated PanIN lesions . This implies that IPMNs of the gastric type/PanIN -1 lesions are not innocuous lesions but have a malignant potential . Summary and perspectives The significance of IPMNs among the pancreatic tumors has increased greatly in recent years because of their improved recognition , both clinically and histopathologically and their much better prognosis than ordinary ductal adenocarcinomas . Moreover , they appear to fall into four subtypes that have special biological properties with prognostic implications . Of particular interest in relation to the development of ductal adenocarcinomas is the fact that the so-called gastric type IPMNs seems to occur in pancreata from patients with a strong family history of pancreatic cancer . Furthermore , it is of interest that the pancreatic IPMNs have their counterparts in IPMNs of the biliary duct system , where the same subtypes may occur -LSB- 1 , 23 , 51 , 52 -RSB- . The treatment of choice is resection , but future trials may reveal that the extent of resection could depend on the IPMN subtype .

O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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