Metachronous peritoneal metastases in patients with pT4b colon cancer: An international multicenter analysis of intraperitoneal versus retroperitoneal tumor invasion.

BACKGROUND: It was hypothesized that colon cancer with only retroperitoneal invasion is associated with a low risk of peritoneal dissemination. This study aimed to compare the risk of metachronous peritoneal metastases (mPM) between intraperitoneal and retroperitoneal invasion. METHODS: In this international, multicenter cohort study, patients with pT4bN0-2M0 colon cancer who underwent curative surgery were categorized as having intraperitoneal invasion (e.g. bladder, small bowel, stomach, omentum, liver, abdominal wall) or retroperitoneal invasion only (e.g. ureter, pancreas, psoas muscle, Gerota's fascia). Primary outcome was 5-year mPM cumulative rate, assessed by Kaplan-Meier analysis. RESULTS: Out of 907 patients with pT4N0-2M0 colon cancer, 198 had a documented pT4b category, comprising 170 patients with intraperitoneal invasion only, 12 with combined intra- and retroperitoneal invasion, and 16 patients with retroperitoneal invasion only. At baseline, only R1 resection rate significantly differed: 4/16 for retroperitoneal invasion only versus 8/172 for intra- +/- retroperitoneal invasion (p = 0.010). Overall, 22 patients developed mPM during a median follow-up of 45 months. Two patients with only retroperitoneal invasion developed mPM, both following R1 resection. The overall 5-year mPM cumulative rate was 13% for any intraperitoneal invasion and 14% for retroperitoneal invasion only (Log Rank, p = 0.878), which was 13% and 0%, respectively, in patients who had an R0 resection (Log Rank, p = 0.235). CONCLUSION: This study suggests that pT4b colon cancer patients with only retroperitoneal invasion who undergo an R0 resection have a negligible risk of mPM, but this is difficult to prove because of its rarity. This observation might have implications regarding individualized follow-up.

Body Image as a Potential Motivator for Bariatric Surgery: a Case-Control Study.

BACKGROUND: Not every eligible person opts for bariatric surgery. Body image concerns might be a reason to choose surgery. This case-control study evaluated differences in body image between a pre-bariatric surgery population and a weight-matched control group from the general population. We hypothesized that the pre-bariatric group would show less satisfaction with appearance, defined as a discrepancy between evaluating one's appearance as less attractive while attaching more importance to appearance. METHODS: Data from 125 pre-bariatric patients were compared with 125 body weight-matched controls from the general population. The Multidimensional Body-Self Relations Questionnaire-Appearance Scales was used to assess appearance evaluation (AE), appearance orientation (AO), and their discrepancy score. Both groups were compared with norms from the non-body weight-matched general population. RESULTS: The pre-bariatric group had lower AE scores (mean 2.23 ± 0.65 vs. mean 2.54 ± 1.06) and higher AO scores (mean 3.33 ± 0.69 vs. mean 3.04 ± 0.90) than the control group. The discrepancy between AE and AO was larger in the pre-bariatric group (p < 0.001). Compared with the general population, both groups showed lower AE scores (d = - 1.43 and d = - 1.12, p < 0.001) and lower AO scores (d = - 0.23 and d = - 0.58, p < 0.001). CONCLUSIONS: People with morbid obesity have on average less body image satisfaction. The results indicate that part of the motivation of people that choose bariatric surgery may be due to relatively low global appearance evaluation combined with considering appearance more important. Knowledge about motivations can be used to communicate realistic expectations regarding treatment outcome.

Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results.

BACKGROUND: The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS: Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2 ). RESULTS: Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2 ) and four at dose level 3 (75 mg/m2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION: Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.

ANTECEDENTES: El papel de la cirugía citorreductora (cytoreductive surgery, CRS) combinado con la quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) en el cáncer gástrico no está definido. Este estudio fase I-II no aleatorizado de escalado de dosis fue diseñado para evaluar la seguridad y la viabilidad de HIPEC, después de la quimioterapia sistémica, en pacientes con cáncer gástrico con diseminación peritoneal limitada. Además, se exploró la máxima dosis tolerada (maximum tolerated dose, MTD) de docetaxel intraperitoneal normotérmico en combinación con una dosis fija de oxaliplatino intraperitoneal. MÉTODOS: Se incluyeron pacientes con adenocarcinoma gástrico cT3-cT4a resecable con metástasis peritoneales limitadas y/o citología peritoneal positiva. Se utilizó una técnica HIPEC abierta con 460 mg/m2 de oxaliplatino hipertérmico (30 minutos) seguido de docetaxel normotérmico (90 minutos) en dosis crecientes (0, 50, 75 mg/m2 ). RESULTADOS: Entre 2014 y 2017, se incluyeron 37 pacientes. De los 25 pacientes que completaron la totalidad del protocolo del estudio, 4 pacientes fueron tratados en el nivel de dosis 1 (0 mg/m2 de docetaxel), 6 pacientes en el nivel de dosis 2 (50 mg/m2 ) y 4 pacientes en el nivel de dosis 3 (75 mg/m2 ). En el nivel de dosis 3, se produjeron dos casos de toxicidad limitante de dosis (dose-limiting toxicities, DLTs), ambas asociadas con un íleo postoperatorio. Posteriormente, otros 11 pacientes fueron tratados con el nivel de dosis 2, y no se produjeron más DLTs. La MTD de docetaxel intraperitoneal fue de 50 mg/m2 . Se registraron efectos adversos graves en 17 de 25 pacientes. La tasa de reoperación fue del 16% (n = 4) y la mortalidad relacionada con el tratamiento fue del 8% (n = 2; ambos en el nivel de dosis 3).

The impact of radiological retroperitoneal lymphadenopathy on survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases.

OBJECTIVES: To investigate the impact of retroperitoneal lymphadenopathy (RPLP) on pre-operative CT scan on overall survival (OS) and disease-free survival (DFS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastases (PM) of colorectal cancer. BACKGROUND: In patients with PM enlarged retroperitoneal lymph nodes (RPLP) are usually considered extra-regional lymph node metastases and therefore these patients may be excluded from CRS-HIPEC. This is a clinical dilemma since it is often hard to obtain histology from these nodes. METHODS: In this multicenter, retrospective study all consecutive patients with colorectal PM treated with CRS-HIPEC between 2004 and 2013 were included. The preoperative CT-scan was re-analyzed for the presence of RPLP based on the radiological appearance of enlarged lymph nodes. Outcomes were OS and DFS. Kaplan-Meier methods and Cox regression modeling were used to analyze the impact of RPLP on OS and DFS. RESULTS: In 25 of 401 patients (6.1%) RPLP was observed on the preoperative CT-scan. Patient, tumor and surgical characteristics did not statistically significantly differ between groups with and without RPLP. After a median follow-up of 46 months, the one-, three- and five-year survival was 80%, 59%, 38% and 90%, 50%, 36% in the group with and without RPLP respectively. Median OS (47 vs. 35 months, logrank: p = 0.70) and median DFS (14 vs. 15 months, logrank: p = 0.81) did not statistically significantly differ between groups. In multivariable analysis, RPLP did not significantly influence survival. CONCLUSION: Enlarged retroperitoneal lymph nodes on a pre-operative CT-scan should not automatically exclude patients from CRS-HIPEC.

Acute cholecystitis in elderly patients: A case for early cholecystectomy.

BACKGROUND: Recent advances in laparoscopic techniques and perioperative care have changed the indications for surgery in elderly patients. Consequently, the willingness to offer early surgery for acute cholecystitis continues to increase. This study aims to assess the perioperative outcome of early cholecystectomy for acute calculous cholecystitis in elderly patients. PATIENTS AND METHODS: All consecutive patients treated by early cholecystectomy for acute calculous cholecystitis in a major teaching hospital, between January 2002 and November 2016, were retrospectively analyzed. The outcome of elderly patients (≥75 years) was compared to that of all others. Conversion rate, 30 days morbidity, 30 days mortality and length of hospital stay were assessed. RESULTS: Early cholecystectomy for acute calculous cholecystitis was performed in 703 patients: 121 (17%) aged ≥75 years and 582 (83%) aged <75 years. Significantly more elderly patients had an ASA score ≥3 (37% vs. 8%, P<0.001). Morbidity was higher in the elderly group (17% vs. 8%, P<0.004), mainly attributable to the high incidence of cystic stump leakage in this group; a complication that no longer occurred after changing the technique of ligation of the cystic stump. The cardiopulmonary complication rate (4% vs. 3%, P=0.35) as well as mortality did not significantly differ (3% vs. 1%, P=0.07). The conversion rate was higher in the elderly group (18% vs. 5%, P<0.001) and the median postoperative length of hospital stay was longer (5.0 vs. 3.0 days, P<0.001). CONCLUSION: Early laparoscopic cholecystectomy is a treatment well suited to elderly patients with mild and moderate acute cholecystitis.

Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis.

BACKGROUND: Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the effect of extended antibiotic prophylaxis on infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. METHODS: For this randomized controlled non-inferiority trial, adult patients with mild acute calculous cholecystitis undergoing cholecystectomy at six major teaching hospitals in the Netherlands, between April 2012 and September 2014, were assessed for eligibility. Patients were randomized to either a single preoperative dose of cefazolin (2000 mg), or antibiotic prophylaxis for 3 days after surgery (intravenous cefuroxime 750 mg plus metronidazole 500 mg, three times daily), in addition to the single dose. The primary endpoint was rate of infectious complications within 30 days after operation. RESULTS: In the intention-to-treat analysis, three of 77 patients (4 per cent) in the extended antibiotic group and three of 73 (4 per cent) in the standard prophylaxis group developed postoperative infectious complications (absolute difference 0·2 (95 per cent c.i. -8·2 to 8·9) per cent). Based on a margin of 5 per cent, non-inferiority of standard prophylaxis compared with extended prophylaxis was not proven. Median length of hospital stay was 3 days in the extended antibiotic group and 1 day in the standard prophylaxis group. CONCLUSION: Standard single-dose antibiotic prophylaxis did not lead to an increase in postoperative infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy. Registration number: NTR3089 (www.trialregister.nl).

Anticipation of complications after laparoscopic cholecystectomy: prediction of individual outcome.

BACKGROUND: Complication rates after a laparoscopic cholecystectomy are still up to 10 %. Knowledge of individual patient risk profiles could help to reduce morbidity. AIM: The aim of this study is to create risk profiles for specific complications to anticipate on individual outcome. PATIENTS AND METHODS: Individual patient outcome for a specific post-operative complication was assessed from a retrospective database of two major teaching hospitals, using uni- and multivariable analyses. RESULTS: A total of 4359 patients were included of which 346 developed one or more complications (8 %). Five risk profiles were found to predict specific complications: older patients (>65 year) are at risk for pneumonia (OR 7.0, 95 % CI 3.3-15.0, p < 0.001) and bleeding (OR 2.2, 95 % CI 1.2-3.9, p = 0.014), patients with acute cholecystitis are at risk for intra-abdominal abscess (OR 5.9, 95 % CI 3.4-10.1, p < 0.001), bile leakage (OR 3.6, 95 % CI 2.0-6.6, p < 0.001) and pneumonia (OR 3.5, 95 % CI 1.6-7.6, p < 0.002), previous history of cholecystitis is predictive for wound infection (OR 5.1, 95 % CI, (2.7-9.7), p < 0.001), intra-abdominal abscess (OR 6.1, 95 % CI 2.8-13.8, p < 0.001), post-operative bleeding (OR 4.8, 95 % CI 2.1-11.1, p < 0.001), bile leakage (OR 7.2, 95 % CI 3.4-15.4, p < 0.001) and pneumonia (OR 3.9, 95 % CI 1.3-11.9, p = 0.018), pre-operative ERCP is predictive for intra-abdominal abscess (OR 3.3, 95 % CI 2.0-5.7, p < 0.001), post-operative bleeding (OR 2.1, 95 % CI 1.2-3.9, p = 0.058) and pneumonia (OR 3.8, 95 % CI 1.9-7.8, p = 0.001), and converted patients are at risk for wound infection (OR 4.0, 95 % CI 2.1-7.7, p < 0.001) and intra-abdominal abscess (OR 3.5, 95 % CI 1.6-7.7, p = 0.002). CONCLUSION: Individual risk prediction of outcome after laparoscopic cholecystectomy is feasible. This facilitates individual pre-operative doctor-patient communication and may tailor surgical strategies.

Semiphysiologically based pharmacokinetic model for midazolam and CYP3A mediated metabolite 1-OH-midazolam in morbidly obese and weight loss surgery patients.

This study aimed to describe the pharmacokinetics of midazolam and its cytochrome P450 3A (CYP3A) mediated metabolite 1-OH-midazolam in morbidly obese patients receiving oral and i.v. midazolam before (n = 20) and one year after weight loss surgery (n = 18), thereby providing insight into the influence of weight loss surgery on CYP3A activity in the gut wall and liver. In a semiphysiologically based pharmacokinetic (semi-PBPK) model in which different blood flow scenarios were evaluated, intrinsic hepatic clearance of midazolam (CLint,H) was 2 (95% CI 1.40-1.64) times higher compared to morbidly obese patients before surgery (P < 0.01). Midazolam gut wall clearance (CLint,G) was slightly lower in patients after surgery (P > 0.05), with low values for both groups. The results of the semi-PBPK model suggest that, in patients after weight loss surgery, CYP3A hepatic metabolizing capacity seems to recover compared to morbidly obese patients, whereas CYP3A mediated CLint,G was low for both populations and showed large interindividual variability.

Sidestream dark field imaging of the serosal microcirculation during gastrointestinal surgery.

AIM: The study aimed to describe the serosal microcirculation of the human bowel using sidestream dark field imaging, a microscopic technique using polarized light to visualize erythrocytes through capillaries. We also compared its feasibility to the current practice of sublingual microcirculatory assessment. METHOD: In 17 patients sidestream dark field measurements were performed during gastrointestinal surgery. Microcirculatory parameters like microvascular flow index (MFI), proportion of perfused vessels (PPV), perfused vessel density (PVD) and total vessel density (TVD) were determined for every patient, sublingually and on the bowel serosa. RESULTS: Sixty measurements were done on the bowel of which eight (13%) were excluded, five owing to too much bowel peristalsis and three because of pressure artefacts. Image stability was in favour of sublingual measurements [pixel loss per image, bowel 145 (95% CI 126-164) vs sublingual 55 (95% CI 41-68); P < 0.001] and time to acquire a stable image [bowel 96 s (95% CI 63-129) vs. sublingual 46 s (95% CI 29-64); P = 0.013]. No difference in the MFI was observed [bowel 2.9 (interquartile range 2.87-2.95) vs sublingual 3.0 (interquartile range 2.91-3.0); P = 0.081]. There was a difference in the PPV [bowel 95% (95% CI 94-96) vs sublingual 97% (95% CI 97-99); P < 0.001], PVD [bowel 12.9 mm/mm2 (95% CI 11.1-14.8) vs sublingual 17.4 mm/mm2 (95% CI 15.6-19.1); P = 0.003] and the TVD [bowel 13.6 mm/mm2 (95% CI 11.6-15.6) vs sublingual 17.7 mm/mm2 (95% CI 16.0-19.4); P = 0.008]. CONCLUSION: Sidestream dark field imaging is a very promising technique for bowel microcirculatory visualization and assessment. It is comparable to sublingual assessment and the analysis produces a similar outcome with slightly differing anatomical features.

Cytoreduction and hyperthermic intraperitoneal chemotherapy: The learning curve reassessed.

BACKGROUND: CytoReductive Surgery and Hyperthermic IntraPEritoneal Chemotherapy (CRS-HIPEC) is now the preferred treatment of many peritoneal surface malignancies. In this retrospective study we aimed to analyze how several performance indicators changed during the first 100 CRS-HIPEC procedures in hospitals which recently introduced this treatment, and compare those with an experienced institution. METHODS: The first consecutive 100 CRS-HIPEC procedures of three institutions were compared to those of the pioneer hospital. The training provided by the pioneer hospital consisted of hands-on training during the first ten procedures; hereafter guidance was available on consult basis. Operation characteristics, morbidity and completeness of cytoreduction were evaluated by case sequence. Locally-estimated-scatter-plot smoothing was used to evaluate the learning curve. RESULTS: From four institutions 372 cases were included. A macroscopic complete cytoreduction was reached in 66% of the cases in the pioneer hospital and in 86% in the new hospitals (p < 0.001). Complete cytoreduction rates were higher at start off in the new institutions compared with the experienced institution and increased significantly in the first 100 procedures. The new hospitals started with lower morbidity than the experienced hospital, which did not significantly decrease during the study period. CONCLUSION: New institutions that were trained and mentored by an experienced CRS-HIPEC hospital performed better from the beginning with regard to complete cytoreduction and morbidity rate with than the experienced center. An improvement in complete cytoreduction rate during the first 100 procedures was observed in the new institutions.

Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer.

PURPOSE: Several studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to provide a comprehensive overview of chemotherapeutic agents used for HIPEC in gastric cancer. METHODS: A literature search was conducted using the PubMed database to identify studies on chemotherapy used for HIPEC in gastric cancer patients. RESULTS AND CONCLUSION: The chemotherapeutic regime of choice in HIPEC for gastric cancer has yet to be determined. The wide variety in studies and study parameters, such as chemotherapeutic agents, dosage, patient characteristics, temperature of perfusate, duration of perfusion, carrier solutions, intraperitoneal pressure and open or closed perfusion techniques, warrant more experimental and clinical studies to determine the optimal treatment schedule. A combination of drugs probably results in a more effective treatment.

Comparison of Imaging Strategies with Conditional versus Immediate Contrast-Enhanced Computed Tomography in Patients with Clinical Suspicion of Acute Appendicitis.

OBJECTIVES: To compare the diagnostic accuracy of conditional computed tomography (CT), i.e. CT when initial ultrasound findings are negative or inconclusive, and immediate CT for patients with suspected appendicitis. METHODS: Data were collected within a prospective diagnostic accuracy study on imaging in adults with acute abdominal pain. All patients underwent ultrasound and CT, read by different observers who were blinded from the other modality. Only patients with clinical suspicion of appendicitis were included. An expert panel assigned a final diagnosis to each patient after 6 months of follow-up (clinical reference standard). RESULTS: A total of 422 patients were included with final diagnosis appendicitis in 251 (60 %). For 199 patients (47 %), ultrasound findings were inconclusive or negative. Conditional CT imaging correctly identified 241 of 251 (96 %) appendicitis cases (95 %CI, 92 % to 98 %), versus 238 (95 %) with immediate CT (95 %CI, 91 % to 97 %). The specificity of conditional CT imaging was lower: 77 % (95 %CI, 70 % to 83 %) versus 87 % for immediate CT (95 %CI, 81 % to 91 %). CONCLUSION: A conditional CT strategy correctly identifies as many patients with appendicitis as an immediate CT strategy, and can halve the number of CTs needed. However, conditional CT imaging results in more false positives. KEY POINTS: • Conditional CT (CT after negative/inconclusive ultrasound findings) can be used for suspected appendicitis. • Half the number of CT examinations is needed with a conditional strategy. • Conditional CT correctly identifies as many patients with appendicitis as immediate CT. • Conditional imaging results in more false positive appendicitis cases.

Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology.

BACKGROUND: Signet ring cell cancer (SRCC) patients have a poor oncologic outcome. The aim of this study was to determine whether the potential drawbacks of hyperthermic intraperitoneal chemotherapy (HIPEC) outweigh the benefits in patients with peritoneally metastasized SRCC. METHODS: Patients with peritoneal carcinomatosis (PC) of colorectal origin referred to two tertiary centers between April 2005 and December 2013 were identified and retrospectively analyzed. Data were compared between SRCC histology and other differentiations. RESULTS: Three-hundred-fifty-one patients were referred for CRS+HIPEC among which 20 (5.7%) patients were identified with SRCC histology. CRS + HIPEC was performed in 16 of these 20 (80%) and 252 out of the 331 remaining patients (76.1%). A higher proportion of patients in the SRCC-group were diagnosed with N2 stage (62.5% vs. 36.1%, P=0.04). A macroscopic complete resection was achieved in 87.5% and 97.2% respectively (P=0.04). Median survival was 14.1 months compared to 35.1 months (P<0.01). Recurrence occurred in 68.8% of the SRCC patients and in 43.7% of the other histology patients (P=0.05). CONCLUSION: Patients with SRCC and PC treated with CRS+HIPEC have a poor median survival only slightly reaching over 1 year. In the presence of other relative contraindications, SRCC histology should refrain a surgeon from performing CRS and HIPEC.

Peritoneal cancer patients not suitable for cytoreductive surgery and HIPEC during explorative surgery: risk factors, treatment options, and prognosis.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the only curative option for patients with peritoneal carcinomatosis of colorectal origin. Despite meticulous preoperative assessment, CRS and HIPEC appear to be impossible in a subset of patients at the time of surgery. This study investigated which clinical factors may identify these patients before surgery and reported on factors influencing survival. METHODS: All patients with PC of colorectal origin between April 2005 and November 2013 who underwent exploratory surgery to determine whether cytoreduction and HIPEC was feasible were included in this study. Details concerning preoperative patient characteristics, perioperative outcomes, treatment and survival were compared. RESULTS: In total, 350 patients with PC were referred to evaluate the possibility of CRS + HIPEC of which 268 (76.6 %) underwent CRS and HIPEC and 82 (23.4 %) had an open-close procedure. The main reason for discontinuing surgery was widespread peritoneal disease (50 %). A preoperative ostomy and an ASA score of 3 were associated with an increased risk for "open and close" (O&C). Median survival was 11.2 months in patients treated with palliative chemotherapy (75 %) compared with 2.7 months with palliative care only. CONCLUSIONS: CRS and HIPEC were deemed unsuitable in almost a quarter of all patients undergoing surgery. No strong clinical predictors for O&C were found, stressing the need for better preoperative imaging modalities. Survival in these patients is limited, but the majority could be treated with palliative chemotherapy resulting in survival of almost 1 year.

The predictive value of proteinuria in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis has a highly variable clinical course. Early and reliable predictors for the severity of acute pancreatitis are lacking. Proteinuria appears to be a useful predictor of disease severity and outcome in a variety of clinical conditions. This study aims to investigate the predictive value of proteinuria on admission for the severity of acute pancreatitis compared with other commonly used predictors; the APACHE II score, Modified Glasgow score and C-reactive protein (CRP). METHODS: This is a post-hoc analysis of 64 patients admitted with acute pancreatitis treated in one teaching hospital, who participated in a previous randomized trial. Proteinuria was defined as a Protein/Creatinine (P/C) ratio >23 mg/mmol. The primary endpoint was severe acute pancreatitis. Secondary endpoints included infectious complications, need for invasive intervention, ICU stay and in-hospital mortality. RESULTS: Proteinuria was present in 30/64 patients (47%). Eleven patients (17%) had severe acute pancreatitis. There was no difference in incidence of severe acute pancreatitis between patients with and without proteinuria: 6/30 patients (20%) versus 5/34 patients (15%) respectively (p = 0.58). Likewise, the occurrence of infectious complications, need for intervention and ICU stay and mortality did not differ significantly (p = 0.58, p = 0.99, p = 0.33 and p = 0.60 respectively). The diagnostic performance of the P/C ratio for the prediction of severe pancreatitis was inferior to the Modified Glasgow score (p = 0.04) and CRP (p = 0.03). CONCLUSION: Proteinuria on admission does not seem to be a reliable predictor for disease severity in acute pancreatitis. The diagnostic performance of the P/C ratio is inferior to the Modified Glasgow score and CRP.

Routine colonoscopy is not required in uncomplicated diverticulitis: a systematic review.

BACKGROUND: It is generally accepted that patients following an episode of diverticulitis should have additional colonoscopy screening to rule out a colorectal malignancy. We aimed to investigate the rate of CRC found by colonoscopy after an attack of uncomplicated diverticulitis. METHODS: MEDLINE, Embase, and Cochrane databases were searched systematically for clinical trials or observational studies on colonic evaluation by colonoscopy after the initial diagnosis of acute uncomplicated diverticulitis, followed by hand-searching of reference lists. RESULTS: Nine studies met the inclusion criteria and included a total number of 2,490 patients with uncomplicated diverticulitis. Subsequent colonoscopy after an episode of uncomplicated diverticulitis was performed in 1,468 patients (59%). Seventeen patients were diagnosed with CRC, having a prevalence of 1.16% (95% confidence interval 0.72-1.9% for CRC). Hyperplastic polyps were seen in 156 patients (10.6%), low-grade adenoma in 90 patients (6.1%), and advanced adenoma was reported in 32 patients (2.2%). CONCLUSION: Unless colonoscopy is regarded for screening in individuals aged 50 years and older, routine colonoscopy in the absence of other clinical signs of CRC is not required.

Peritoneal carcinomatosis in t4 colorectal cancer: occurrence and risk factors.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy improves outcome of patients with peritoneal carcinomatosis (PC) of colorectal carcinoma. Data on the occurrence of PC in T4 colorectal carcinoma are scarce. We investigated the occurrence and risk factors for PC in these patients. METHODS: This was a retrospective cohort study of patients undergoing a first resection of a T4 colorectal carcinoma in a tertiary hospital between January 2000 and December 2007. Primary outcome was the occurrence of synchronous or metachronous PC. The association with PC and several patient and tumor characteristics was evaluated using logistic regression. RESULTS: A total of 200 patients underwent resection of a T4 colorectal carcinoma. Median follow-up censored for death was 66 months (18-89 months). Synchronous PC was found in 46 of 200 patients (23 %) and metachronous PC in 33 of 154 patients (21 %). In univariable analysis, factors associated with PC were: age (OR 0.97; 95 % CI 0.94-0.99; P = 0.03), radical resection (OR 0.32; 95 % CI 0.11-0.91; P = 0.03), and N stage (OR 1.63; 95 % CI 1.36-2.34; P = 0.008). In multivariable analysis, only N stage was associated with PC (OR 1.62; 95 % CI 1.12-2.34; P = 0.01). This association was not significant for the 154 patients at risk for metachronous PC. CONCLUSIONS: Around 1 in 5 patients undergoing resection of a T4 colorectal carcinoma either have PC during primary resection or develop PC during follow-up. N stage was associated with PC in the entire study population. However, none of the clinical or pathological variables were associated with the risk of metachronous PC and therefore cannot be used to develop targeted surveillance strategies.

An integrated population pharmacokinetic meta-analysis of propofol in morbidly obese and nonobese adults, adolescents, and children.

This study describes a population pharmacokinetic meta-analysis of propofol to characterize the influence of body size measures and age in morbidly obese and nonobese adults, adolescents, and children. Sixty morbidly obese and nonobese adult patients (55-167 kg; 21-79 years) and 34 morbidly obese and nonobese adolescents and children (37-184 kg; 9-20 years) were included. The results show that clearance increased with total body weight in an allometric function while age was found to influence clearance in a bilinear fashion with two distinct slopes, reflecting an initial increase and subsequent decrease as a result of aging. Using these two functions, the influence of both (over)weight and age on propofol clearance was well characterized, which may provide a basis for dosing across this diverse group of patients.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e73; doi:10.1038/psp.2013.47; advance online publication 11 September 2013.

Hyperthermic intraperitoneal chemotherapy during primary tumour resection limits extent of bowel resection compared to two-stage treatment.

AIM: To compare the clinical outcome of a one-stage, primary tumour resection and hyperthermic intraperitoneal chemotherapy (HIPEC) procedure, versus a two-stage procedure of tumour resection and secondary HIPEC in colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis. METHODS: A prospective database of all patients treated with HIPEC in the St. Antonius Hospital in the Netherlands between 2005 and 2012 was analysed. RESULTS: A total of 72 patients with synchronous peritoneal carcinomatosis (PC) from CRC were included. In 20 patients (27.8%) the primary tumour was resected simultaneously with HIPEC (early referral). In the other 52 patients (72.2%) the primary tumour was resected prior to the HIPEC procedure (late referral). During CRS + HIPEC following late referral, 22 (59.5%) of the 37 anastomoses of the earlier operation were resected, revealing malignancy in 12 (54.5%) on histopathological examination. In twenty (27.8%) patients a permanent colostomy was constructed after HIPEC. Ten of these patients had complete bowel continuity after earlier primary resection. The relaparotomy rate was higher in patients after a resection of a previous anastomosis (36.4%) compared to 12% in the rest of the patients (P = 0.02). CONCLUSIONS: Resection of the primary tumour simultaneously with HIPEC in patients with synchronous PC from CRC may prevent extended bowel resections and permanent colostomy. Our data support early referral of patients with PC from colorectal cancer.