Diffuse Malignant Peritoneal Mesothelioma: Failure Analysis Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumor ≤2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6–35.9]. Median survival from progression was 8 months (95% CI 4–16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumor ≤2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression <9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.     

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m²) or mitomycin C (35 mg/m²). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.     

Complete Cytoreduction and HIPEC Improves Survival in Desmoplastic Small Round Cell Tumor

Background

Desmoplastic small round cell tumor (DSRCT) is a rare tumor of adolescents and young adults. Less than 100 cases per year are reported in North America. Extensive peritoneal metastases are characteristic of this disease. We performed cytoreductive surgery and hyperthermic peritoneal perfusion with chemotherapy (HIPEC) using cisplatin (CDDP) for DSRCT.

Methods

A retrospective cohort study was performed on 26 pediatric and adult patients who underwent cytoreduction/HIPEC using CDDP for DSRCT at a single cancer center. Neoadjuvant chemotherapy, adjuvant chemotherapy, and postoperative enteral nutrition were given to all patients. Postoperative radiation therapy was given to most patients. Follow-up was from 6 months to 6 years. Outcome variables were evaluated for disease-free and overall survival (OS).

Results

Five patients (19 %) were less than 12 years of age at surgery. Patients who had disease outside the abdomen at surgery had a larger risk of recurrence or death than those who did not (p = 0.0158, p = 0.0393 time from surgery to death respectively). Age, liver metastasis, and peritoneal cancer index level did not significantly predict disease-free or OS. Patients who had CR0 or CR1 and HIPEC had significantly longer median survival compared with patients who had HIPEC and CR2 cytoreduction (63.4 vs. 26.7 months).

Conclusions

HIPEC may be an effective therapy for children and young adults with DSRCT. Patients with DSRCT require complete cytoreduction before HIPEC to optimize outcome. Patients with DSRCT and disease outside the abdomen at the time of surgery do not benefit from HIPEC.     

Incidence and Treatment of Tracheal Cancer: A Nationwide Study in The Netherlands

Background The aim of this study was to assess the incidence, characteristics, treatment, and survival of patients with tracheal malignancies in the Netherlands. Methods All cases of tracheal cancer entered into the database of the Netherlands Cancer Registry in the period 1989–2002 were selected. Data on histological type, age at time of diagnosis, treatment, and survival were analyzed retrospectively. Results The annual incidence was 0.142 per 100,000 inhabitants (308 cases, of which 15 were found incidentally at autopsy). Of these, 72% were men. In 52.9%, the histological type was squamous cell carcinoma and in only 7.1% adenoid cystic carcinoma (ACC). Mean age at time of diagnosis was 64.3 years. Of the 293 patients diagnosed while alive, 34 patients underwent surgical resection (11.6%), 156 patients received radiotherapy (53.2%), and 103 patients neither (35.4%). Median survival of all 293 patients was 10 months (mean 28 months) with 1-year, 5-year, and 10-year survival rates of 43%, 15%, and 6%, respectively. The prognosis of patients with ACC was significantly better. The 5-year survival rate in patients who underwent surgical resection was 51%, and the 10-year survival rate in these patients was 33%. Conclusion The prognosis of patients with a tracheal malignancy is usually poor. Surgical treatment, however, can lead to good survival rates; still, this is currently only used in selected patients, even though it would seem to be possible in more cases in view of the technical advances in the field of tracheal surgery. Centralizing the care and treatment of tracheal cancers and implementing a more assertive attitude towards this disease could make surgery accessible to a larger number of patients. Data from the literature show that this would lead to better survival in patients with a tracheal malignancy.     

Nationwide breast cancer screening programme fully implemented in The Netherlands

The period 1990-1997 saw the implementation of a nationwide breast cancer screening programme in the Netherlands, which provided biennial mammography for all women aged 50-69 years (50-75 years at present). The National Evaluation Team monitors the programme annually collecting regional data on screening outcomes; regional cancer registries provide data on interval cancers and on breast cancers in unscreened women by linkage of cancer registry data to data on screened women. Of 4 million women invited, 78.5% attended for screening. Screening resulted in 13.1 referrals, 9.2 biopsies and 6.1 breast cancers detected per 1000 women screened initially (6.9, 4.5 and 3.5 per 1000 in subsequently screened women, respectively). Within the first 2 years following screening 0.95 interval cancers per 1000 women-years were diagnosed. The stage distribution of screen-detected cancers was more favourable than that of interval cancers and of those diagnosed in unscreened women. The results are largely consistent with expectations. Results may nonetheless be further improved, particularly the detection rate in subsequent screens.     

The Relationship between Volume and Outcome after Bariatric Surgery: A Nationwide Study in Taiwan

Background

This study purposed to explore the impact of hospital volume and surgeon volume on hospital resource utilization after bariatric surgery and to identify the predictors of length of stay (LOS) and hospital treatment cost in a nationwide population in Taiwan.

Methods

This population-based cohort study retrospectively analyzed 2,674 bariatric surgery procedures performed from 1997 to 2008. Hospitals were classified as low- and high-volume hospitals if their annual number of bariatric surgeries were <35 and ??35, respectively. Surgeons were classified as low- and high-volume surgeons if their annual number of bariatric surgeries were <15 and ??15, respectively. Hierarchical linear regression models were used to predict LOS and hospital treatment cost.

Results

The mean LOS was 7.67?days and the LOS for high-volume hospitals/surgeons was, on average, 28%/31% shorter than that for low-volume hospitals/surgeons. The mean hospital treatment cost was US$2,344.08, and the average hospital costs for high-volume hospitals/surgeons were 10%/13% lower than those for low-volume hospitals/surgeons. Advanced age, male gender, high Charlson co-morbidity index, and current treatment in a low-volume hospital, by a low-volume surgeon, and via open gastric bypass were significantly associated with long LOS and high hospital treatment cost (P?Conclusions The data suggest that annual surgical volume is the key factor in hospital resource utilization. The results improve the understanding of medical resource allocation for this surgical procedure and can help to formulate public health policies for optimizing hospital resource utilization for related diseases.     

Treatment and Outcome of Synchronous Colorectal Carcinomas: A Nationwide Study

Background

Synchronous colorectal carcinomas (CRC) occur in 1–8% of patients diagnosed with CRC. This study evaluated treatment patterns and patient outcomes in synchronous CRCs compared with solitary CRC patients.

Methods

All patients diagnosed with primary CRC between 2008 and 2013, who underwent elective surgery, were selected from the Netherlands Cancer Registry. Using multivariable regressions, the effects of synchronous CRC were assessed for both short-term outcomes (prolonged postoperative hospital admission, anastomotic leakage, postoperative 30-day mortality, administration of neoadjuvant or adjuvant treatment), and 5-year relative survival (RS).

Results

Of 41,060 CRC patients, 1969 patients (5%) had synchronous CRC. Patients with synchronous CRC were older (mean age 71 ± 10.6 vs. 69 ± 11.4 years), more often male (61 vs. 54%), and diagnosed with more advanced tumour stage (stage III–IV 54 vs. 49%) compared with solitary CRC (all p < 0.0001). In 50% of the synchronous CRCs, an extended surgery was conducted (n = 934). Synchronous CRCs with at least one stage II–III rectal tumour less likely received neoadjuvant (chemo)radiation [78 vs. 86%; adjusted OR 0.6 (0.48–0.84)], and synchronous CRCs with at least one stage III colon tumour less likely received adjuvant chemotherapy [49 vs. 63%; adjusted OR 0.7 (0.55–0.89)]. Synchronous CRCs were independently associated with decreased survival [RS 77 vs. 71%; adjusted RER 1.1 (1.01–1.23)].

Conclusions

The incidence of synchronous CRCs in the Dutch population is 5%. Synchronous CRCs were associated with decreased survival compared with solitary CRC. The results emphasize the importance of identifying synchronous tumours, preferably before surgery to provide optimal treatment.

     

The Prognostic Value of Lymph Node Ratio in Node-Positive Breast Cancer: A Dutch Nationwide Population-Based Study

Background

The absolute number of involved axillary lymph nodes (LNs) is considered the most important prognostic factor in breast cancer. Over the last decade, several studies indicated that the lymph node ratio (LNR) might predict outcome better than the number of positive LNs. In this study we test the applicability of earlier published LNR cutoff values and study the prognostic value of the LNR on a nationwide level.

Methods

A nationwide population-based study was performed, using data from the Netherlands Cancer Registry, including all women diagnosed with node-positive breast cancer between 1999 and 2005 (N = 25,315). Patients were divided into 3 LNR risk groups (low, ≤0.20; intermediate, 0.21–0.65; and high, >0.65). Kaplan–Meier survival analysis was performed. In order to evaluate whether LNR was associated with overall survival (OS), Cox proportional hazards modeling was used.

Results

For the entire cohort, 5- and 10-year OS rates were 78 % and 62 %, respectively. The number of positive LNs correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1–3, 4–9, and 10 or more positive LNs, respectively, P < .001). LNR also correlated with OS (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups, respectively, P < .001). In the multivariable analysis, the risk of death increased with increasing LNR (P < .001).

Conclusions

The LNR has an important prognostic value in node-positive patients, independent of traditional clinicopathological factors. LNR should be added as an independent prognostic variable to the current staging system.     

Variation in Lymph Node Evaluation in Rectal Cancer: A Dutch Nationwide Population-Based Study

Background

For adequate staging and subsequent accurate estimation of prognosis, a sufficient number of lymph nodes (LNs) has to be evaluated. This study aimed to identify factors associated with adequate nodal evaluation and to determine its relationship with survival.

Methods

Data from all patients with stage I to III rectal carcinoma who underwent surgical treatment and who were diagnosed in the period 2000 to 2006 were retrieved from the Netherlands Cancer Registry. Multilevel logistic analysis was performed to examine the influence of relevant factors on the number of evaluated LNs. Kaplan–Meier and Cox regression analyses were used to analyze the association with overall survival.

Results

The number of evaluated LNs was determined for 10,788 (91%) of 11,818 tumors. Median number of evaluated LNs was 7, ranging from 4 to 11 between pathology laboratories. The proportion of patients with positive LNs increased with increasing number of evaluated LNs. Men, younger patients, tumors with deeper invasion and nodal involvement, patients without preoperative radiotherapy who underwent a low anterior resection, and patients whose LNs were evaluated in an academic pathology laboratory were more likely to have ≥12 LNs evaluated. After adding these factors to the model, unexplained variation between pathology laboratories and between hospitals remained. The overall survival increased with increasing number of evaluated LNs.

Conclusions

A large variation in LN evaluation among patients with rectal cancer was revealed. Improvement in LN evaluation by both hospitals and pathology laboratories could improve staging, leading to more reliable estimation of prognosis.     

Long-term functional sequelae of sacrococcygeal teratoma: a national study in The Netherlands

Background

Long-term functional sequelae after resection of sacrococcygeal teratoma (SCT) are relatively common. This study determines the incidence of these sequelae associated clinical variables and its impact on quality of life (QoL).

Patients and methods

Patients with SCT treated from 1980 to 2003 at the pediatric surgical centers in the Netherlands aged more than 3 years received age-specific questionnaires, which assessed parameters reflecting bowel function (involuntary bowel movements, soiling, constipation), urinary incontinence, subjective aspect of the scar, and QoL. These parameters were correlated with clinical variables, which were extracted from the medical records. Risk factors were identified using univariate analysis.

Results

Of the 99 posted questionnaires, 79 (80%) were completed. The median age of the patients was 9.7 years (range, 3.2-22.6 years). There were 46% who reported impaired bowel function and/or urinary incontinence (9% involuntary bowel movements, 13% soiling, 17% constipation), and 31% urinary incontinence. In 40%, the scar was cosmetically unacceptable. Age at completion of the questionnaire, Altman classification, sex, and histopathology were not risk factors for any long-term sequelae. Size of the tumor (>500 cm³) was a significant risk factor for cosmetically unacceptable scar (odds ration [OR], 4.73; confidence limit [CL], 1.21-18.47; P = .026). Long-term sequelae were correlated with diminished QoL.

Conclusion

A large proportion of the patients with SCT have problems with defecation, urinary incontinence, or a cosmetically unacceptable scar that affects QoL. Patients who are at higher risk for the development of long-term sequelae cannot be clearly assessed using clinical variables.     

Operative Re-intervention Following Pancreatic Head Resection: Indications and Outcome

Background  This study analyzed indication and outcome regarding operative re-intervention following pancreatoduodenectomy (PD) and pancreatogastrostomy (PG) with special emphasis on complications related to redo surgery. Patients and Methods  Two hundred eighty-five patients who underwent PD with PG between 1989 and 2008 were identified from a pancreatic resection database and indications for repeat surgery were registered. Patients with and without reoperation were analyzed with regard to gender, age, underlying disease, length of hospital stay, mortality rate, and postoperative complications. Results  Thirty-one patients (11%) underwent operative reintervention. Early intra-abdominal extraluminal postoperative bleeding was the main cause for redo surgery followed by abdominal abscesses. Thirteen percent of patients with and 1.9% without secondary surgery died during the postoperative course. Forty-five percent of reoperated patients had to undergo at least one more operation resulting in doubling of the length of hospital stay. There was no correlation between patients’ gender, age, and underlying disease and the need for operative reintervention. However, redo surgery was associated with higher incidence of delayed gastric emptying, pancreatic fistula and bleeding, and non-surgery related complication. Intra-abdominal bleeding and abscesses, insufficiencies of bilio-digestive and gut anastomosis, wound infections, and pancreatitis were observed significantly more often in patients with secondary surgery. Conclusions  Complications after pancreatic resection that require operative re-intervention are associated with a notably increased mortality, ranging between 13% and 60%. Apart from the surgeon’s experience in selecting patients and his/her personal technical skills in performing a pancreaticoduodenectomy, timely anticipation and determined management of postoperative complications is essential for improving the outcome of this operation.     

The Impact of Discharge Timing on Readmission Following Hepatopancreatobiliary Surgery: a Nationwide Readmission Database Analysis

Objective

Decreasing hospital length-of-stay (LOS) may be an effective strategy to reduce costs while also improving outcomes through earlier discharge to the non-hospital setting. The objective of the current study was to define the impact of discharge timing on readmission, mortality, and charges following hepatopancreatobiliary (HPB) surgery.

Methods

The Nationwide Readmissions Database (NRD) was used to identify patients undergoing HPB procedures between 2010 and 2014. Length of stay (LOS) was categorized as early discharge (4–5 days), routine discharge (6–9 days), and late discharge (10–14 days). Univariable and multivariable analyses were utilized to identify factors associated with 90-day readmission.

Results

A total of 28,114 patients underwent HPB procedures. Overall median LOS was 7 days (IQR 5–11); 10,438 (37.1%) patients had an early discharge, while 13,665 (48.6%) and 4011 (14.3%) patients had a routine or late discharge. The probability of early discharge increased over time (referent 2010: 2011–4% (OR 1.04, 95% CI 0.96–1.15) vs. 2012–10% (OR 1.10, 95% CI 1.01–1.20) vs. 2013–21% (OR 1.21, 95% CI 1.11–1.32) vs. 2014–32% (OR 1.32, 95% CI 1.21–1.44)) (p?<?0.001). Early discharge was associated with insurance status, diagnosis (benign vs. malignant disease), general health, and overall hospital volume (all p?<?0.05). Among patients who had an early discharge, 30- and 90-day readmission was 11.5 and 17.4%, respectively. In contrast, 30- and 90-day readmission was 16.9 and 24.7%, respectively, among patients who had a routine discharge group (p?<?0.001). Among patients readmitted within 90 days, in-hospital mortality was similar among patients who had early (n?=?43, 2.4%) versus routine discharge (n?=?65, 1.9%). Median charges were lower among patients who had an early versus routine versus late discharge ($54,476 [IQR 40,053–79,100] vs. $75,192 [IQR 53,296–113,123] vs. $115,061 [IQR 79,162–171,077], respectively) (p?<?0.001).

Conclusions

Early discharge after HPB surgery was not associated with increased 30- or 90-day readmission. Overall 90-day in-hospital mortality following a readmission was comparable among patients with an early, routine, and late discharge, while median charges were lower in the early discharge group.

     

Surveillance MR Imaging is Superior to Serum Tumor Markers for Detecting Early Tumor Recurrence in Patients with Appendiceal Cancer Treated with Surgical Cytoreduction and HIPEC

Background

The purpose of this study was to determine if MRI surveillance is better than serum tumor makers in detecting early recurrence in patients with mucinous appendiceal neoplasm.

Materials and Methods

A total of 50 patients with appendiceal neoplasm (DPAM 11, PMCA 39) underwent abdominal and pelvic MRI prior to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients then entered follow-up surveillance with serial MRI every 6 months and serial laboratory studies including CA 125, CEA, and CA19-9. Written reports for surveillance MRI exams were reviewed for tumor recurrence and compared with results of serial laboratory tests. Proof of tumor recurrence was by a consensus of surgery and histopathology, as well as clinical and imaging findings on serial examinations.

Results

During surveillance tumor recurrence was documented in 30 patients (60 %) with median time to recurrence of 13 months (range 3–56 months). MRI detected recurrent tumor in 28 patients, including 11 patients with normal laboratory values (sensitivity 0.93, specificity 0.95, accuracy 0.94, PPV 0.97, and NPV 0.90). Serial laboratory values showed tumor recurrence in 14 patients (sensitivity 0.48, specificity 1.00, accuracy 0.69, PPV 1.0, and NPV 0.57). Median survival was 50 months for 11 patients with earlier MRI detection of recurrence vs 33 months for the other 19 patients with recurrence.

Conclusions

Following cytoreductive surgery and HIPEC MRI detects tumor recurrence earlier and with greater accuracy than serial tumor markers alone.     

Incidence and Risk Factors for Mortality Following Bariatric Surgery: a Nationwide Registry Study

Background

Although bariatric surgery (BS) is considered safe, concern remains regarding severe post-operative adverse events and mortality. Using a national BS registry, the aim of this study was to assess the incidence, etiologies, and risk factors for mortality following BS.

Methods

Prospective data from the National Registry of Bariatric Surgery in Israel (NRBS) including age, gender, BMI, comorbidities, and surgical procedure information were collected for all patients who underwent BS in Israel between June 2013 and June 2016. The primary study outcome was the 3.5-year post-BS mortality rate, obtained by cross-referencing with the Israel population registry.

Results

Of the 28,755 patients analyzed (67.3% females, mean age 42.0?±?12.5 years, and preoperative BMI 42.14?±?5.21 kg/m²), 76% underwent sleeve gastrectomy (SG), 99.1% of the surgeries were performed laparoscopically, and 50.8% of the surgeries were performed in private medical centers. Overall, 95 deaths occurred during the study period (146.9/100,000 person years). The 30-day rate of post-operative mortality was 0.04% (n =?12). Male gender (HR?=?1.94, 95%CI 1.16–3.25), age (HR?=?1.06, 95%CI 1.04–1.09), BMI (HR?=?1.08, 95%CI 1.05–1.11), and depression (HR?=?2.38, 95%CI 1.25–4.52) were independently associated with an increased risk of all-cause 3.5-year mortality, while married status (HR?=?0.43, 95%CI 0.26–0.71) was associated with a decreased risk.

Conclusion

Mortality after BS is low. Nevertheless, a variety of risk factors including male gender, advanced age, unmarried status, higher BMI, and preoperative depressive disorder were associated with higher mortality rates. Special attention should be given to these “at-risk” BS patients.