Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Clinical characteristics of patients with pneumatosis intestinalis.

BACKGROUND: Several theories explaining the development of pneumatosis intestinalis (PI) have been reported, but a substantial portion of cases have been idiopathic. Additionally, predictors of bowel ischaemia in PI have not been fully investigated, while PI with bowel ischaemia has deteriorated overall outcomes of PI. METHODS: Sixty-four patients diagnosed with PI (2009-2019) were allocated to two groups: with (group 1; n = 15 (23%)) and without (group 2; n = 49 (77%)) bowel ischaemia. Fourteen patients underwent emergency surgery, and bowel ischaemia was identified in nine (64%). Six patients in group 1 were diagnosed with bowel ischaemia, and were treated palliatively. On medical charts, we determined underlying conditions of PI, compared the characteristics and outcomes between the groups, and identified the predictors of bowel ischaemia. RESULTS: Group 1 patients more commonly showed abdominal pain, lower base excess, higher C-reactive protein concentrations, higher white blood cell counts and higher neutrophil-to-lymphocyte ratios, and more frequent comorbid ascites, free air and hepatic portal vein gas. Of nine bowel ischaemia surgery patients, three (33%) died; all because of anastomotic leak. All except three patients in group 2, who presented with aspiration pneumonia, responded to treatment. Only one patient had an unknown cause (1/64, 1.6%), and various underlying conditions in secondary PI were confirmed. CONCLUSION: Idiopathic PI may be identified rarely using current imaging and knowledge, but outcomes in PI patients with bowel ischaemia remain unsatisfactory. Earlier identification of bowel ischaemia by various specialists in accordance with predictors of bowel ischaemia could improve overall outcomes in PI patients.

Clinical features of patients with hepatic portal venous gas.

BACKGROUND: Hepatic portal venous gas (HPVG) is a rare clinical condition that is caused by a variety of underlying diseases. However, the factors that would permit accurate identification of bowel ischemia, requiring surgery, in patients with HPVG have not been fully investigated. METHODS: Thirty patients that had been diagnosed with HPVG using computed tomography between 2010 and 2019 were allocated to two groups on the basis of clinical and intraoperative findings: those with (Group 1; n = 12 [40%]) and without (Group 2; n = 18 [60%]) bowel ischemia. Eleven patients underwent emergency surgery, and bowel ischemia was identified in eight of these (73%). Four patients in Group 1 were diagnosed with bowel ischemia, but treated palliatively because of their general condition. We compared the characteristics and outcomes of Groups 1 and 2 and identified possible prognostic factors for bowel ischemia. RESULTS: At admission, patients in Group 1 more commonly showed the peritoneal irritation sign, had lower base excess, higher lactate, and higher C-reactive protein, and more frequently had comorbid intestinal pneumatosis. Of the eight bowel ischemia surgery patients, four (50%) died, mainly because of anastomotic leak following bowel resection and primary anastomosis (3/4, 75%). All except one patient in Group 2, who presented with aspiration pneumonia, responded better to treatment. CONCLUSIONS: Earlier identification and grading of bowel ischemia according to the findings at admission should benefit patients with HPVG by reducing the incidence of unnecessary surgery and increasing the use of safer procedures, such as prophylactic stoma placement.

Splenic artery aneurysm rupture during pregnancy: A case report of maternal and fetal survival.

INTRODUCTION: Pregnancy has been demonstrated as a significant risk factor of splenic artery aneurysm (SAA) formation and rupture. However, prompt diagnosis of SAA rupture in a pregnant patient showing acute abdomen has been practically challenging in light of its rarity and vague initial presentation. PRESENTATION OF CASE: A 40-year-old woman (gravida 1, para 0) at 35 weeks' gestation presented to the emergency department with upper abdominal pain and nausea. Because of fetal dysfunction, emergency caesarian section was performed by a Pfannenstiel incision. Following delivery, 400 g of hemorrhage was removed from the upper abdominal cavity. Computed tomography showed a 37-mm SAA associated with copious adjacent fluid. Although selective angiography did not demonstrate active extravasation, interventional isolation of the SAA was not performed because of multiple surrounding arteries. Relaparotomy with an upper midline incision was then performed. Sudden cardiac arrest occurred upon opening the lesser sac to irrigate clots, and cardiac massage and proximal and distal clamping of the SAA were required. Eventually, splenectomy with excision of the SAA and pancreatic tail was successfully performed, but gauze packing of the open surgical wound was required because of severe coagulopathy. Following removal of the packs and closure of the abdomen 2 days after splenectomy, the patient and infant satisfactorily recovered without sequelae. DISCUSSION: Given continual awareness of abdominal vascular collapse during pregnancy, undelayed diagnosis and safer intervention might be achieved. CONCLUSION: Awareness at initial presentation and multidisciplinary efforts might be essential to achieve maternal and fetal survival in SAA rupture during pregnancy.

Oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases.

BACKGROUND: The oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases (SLLM) have not been fully investigated. METHODS: Patients undergoing initial hepatectomy for colorectal liver metastases (CLM) from 2005 to 2016 were divided into three groups: patients with isolated CLM undergoing complete resection (Group1, n = 317), SLLM undergoing complete metastasectomy (Group2, n = 33), and SLLM undergoing complete hepatectomy but incomplete lung resection (Group3, n = 20). A staged strategy (hepatectomy followed by lung resection) without interval chemotherapy was mainly applied for SLLM. RESULTS: The 5-year overall survival rate of Group2 was significantly better than that of Group3 (71.7% vs. 10.2%, P < 0.001) and similar to that of Group1 (63.9%, P = 0.779). The 5-year disease-free survival rate was significantly worse in Group2 than Group1 (15.7% vs. 29.0%, P = 0.035). On multivariable analysis, CEA>200 ng/ml was the sole predictor of incomplete resection of lung metastases (odds ratio, 13.7; 95% confidence interval, 1.30-145; P = 0.011). CONCLUSIONS: The prognosis in patients with SLLM who achieve complete metastasectomy is acceptable and might be improved by appropriate selection based on operative indications.

APC and PIK3CA Mutational Cooperativity Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colorectal Liver Metastases.

OBJECTIVE: The aim of the study was to determine the prognostic impact of co-existence of APC and PIK3CA mutations in patients undergoing preoperative chemotherapy and resection for colorectal liver metastases (CLM). BACKGROUND: Co-occurring genetic events have been shown to drive carcinogenesis in multiple malignancies. METHODS: We identified 396 patients with primary colorectal cancer and known somatic mutation status by next-generation sequencing who underwent hepatectomy for CLM (2005-2015). Survival after hepatectomy in patients with double mutation of APC and PIK3CA and others was analyzed. Predictors of pathologic response and survival were determined. The prognostic value of double mutation was evaluated with a separate cohort of 157 patients with CLM undergoing chemotherapy alone. RESULTS: Forty-five patients had double mutation of APC and PIK3CA; 351 did not. Recurrence-free survival (RFS) and overall survival (OS) after hepatectomy were worse in patients with double mutation (3-year RFS, 3.1% vs 20% [P < 0.001]; 3-year OS, 44% vs 84% [P < 0.001]). Independent predictors of major pathologic response were bevacizumab use (odds ratio [OR] 2.22; P = 0.001), tumor size <3 cm (OR 1.97; P = 0.004), wild-type RAS (OR 2.00; P = 0.003), and absence of double mutation (OR 2.91; P = 0.002). Independent predictors of worse OS were primary advanced T category (hazard ratio [HR] 2.12; P = 0.021), RAS mutation (HR 1.74; P = 0.015), and double mutation (HR 3.09; P < 0.001). In the different medical cohort, patients with double mutation had worse 3-year OS of 18%, compared with 35% without double mutation (P = 0.023). CONCLUSIONS: Double mutation of APC and PIK3CA predicts inferior response to preoperative chemotherapy and poor survival in patients with CLM.

Deleterious Effect of RAS and Evolutionary High-risk TP53 Double Mutation in Colorectal Liver Metastases.

OBJECTIVE: To assess the impact of somatic gene mutations on survival among patients undergoing resection of colorectal liver metastases (CLM). BACKGROUND: Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk stratification is necessary to optimize patient selection for surgery. METHODS: Next-generation sequencing of 50 cancer-related genes was performed from primary tumors and/or liver metastases in 401 patients undergoing CLM resection. Missense TP53 mutations were classified by the evolutionary action score (EAp53)-a novel approach that dichotomizes mutations as low or high risk. RESULTS: The most frequent somatic gene mutations were TP53 (65.6%), followed by KRAS (48.1%) and APC (47.4%). Double mutation in RAS/TP53, identified in 31.4% of patients, was correlated with primary tumor location in the right colon (P = 0.006). On multivariable analysis, RAS/TP53 double mutation was an independent predictor of shorter overall survival (hazard ratio 2.62, 95% confidence interval 1.41-4.87, P = 0.002). In patients with co-mutated RAS, EAp53 high-risk mutations were associated with shorter 5-year overall survival of 12.2%, compared with 55.7% for TP53 wild type (P < 0.001). The negative prognostic effects of RAS and TP53 mutations were limited to tumors harboring mutations in both genes. CONCLUSIONS: Concomitant RAS and TP53 mutations are associated with decreased survival after CLM resection. A high EAp53 predicts a subset of patients with worse prognosis. These preliminary analyses suggest that surgical resection of liver metastases should be carefully considered in this subset of patients.

RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases.

OBJECTIVE: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). BACKGROUND: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. METHODS: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. RESULTS: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. CONCLUSIONS: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Liver Resection for Hepatocellular Carcinoma in Patients with Renal Dysfunction.

BACKGROUND: The aim of this study was to evaluate the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with preoperative renal dysfunction (RD). METHODS: Data from 735 patients undergoing primary liver resection for HCC between 2002 and 2014 were analyzed. Short- and long-term outcomes were compared between the RD group, defined by a preoperative estimated glomerular filtration rate of <45 mL/min/1.73 m2, and the non-RD group. RESULTS: Sixty-two patients had RD. The incidence of postoperative pleural effusion (24 vs. 11%; P = 0.007) and major complications (Clavien-Dindo III-V; 31 vs. 15%; P = 0.003) were significantly higher in RD patients. In RD patients with Child-Pugh A, 90-day mortality rate (1.9%) and median survival time (6.11 years) were comparable to that of non-RD patients. In contrast, RD patients with Child-Pugh B had a very high 90-day mortality rate (22.2%), and a significant shorter median survival time compared to non-RD patients (1.19 vs. 4.84 years; P = 0.001). CONCLUSIONS: Liver resection for Child-Pugh A patients with RD is safe and has comparable oncological outcomes compared to non-RD patients. However, selection of liver resection candidates from Child-Pugh B patients with RD should be stricter.

Contrast-enhanced intraoperative ultrasound in the resection of colorectal liver metastases with intrabiliary growth.

A 68-year-old male who had undergone low anterior resection for primary rectal cancer 19 months ago presented with multiple CLM at Couinaud's segments IV, V, and VIII. There was no apparent macroscopic intrabiliary growth on preoperative computed tomography and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). However, the hepatobiliary phase of EOB-MRI revealed peritumoral low signal intensity in lesions in segments V and VIII, which indicates vascular invasion around hepatocellular carcinoma. Contrast-enhanced intraoperative ultrasound (CE-IOUS) clearly determined the extent of macroscopic glissonean growth from lesions in segments V and VIII, and more extensive resection was performed than was planned. Analysis of the resected specimens from segments V and VIII confirmed the presence of macroscopic intrabiliary growth with microscopic portal vein invasion. All three CLM were histopathologically diagnosed as well-to-moderately differentiated adenocarcinoma, and R0 resection was verified. Postoperative recovery was uneventful, and the patient was alive without evidence of recurrence 12 months after hepatic resection. CE-IOUS should be considered at the time of CLM resection, as it might enable more accurate detection of macroscopic intrabiliary growth of CLM, and enable resection with safer margins.

Endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy: A case report.

Malignant transformation of diaphragmatic endometriosis is rare. We present a case of endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy. A 59-year-old primigravida woman who had undergone abdominal hysterectomy for adenomyosis at the age of 47 years was referred to our hospital for investigation of a tumor on the surface of the liver. An integrated positron emission tomography-computed tomography scan revealed a 3-cm nodule on the surface of the liver with abnormal fluorine-18-deoxyglucose accumulation. Partial resection of the diaphragm and liver was performed. Histopathological examination revealed an endometrioid carcinoma arising from diaphragmatic endometriosis. We additionally performed laparoscopic bilateral salpingo-oophorectomy and partial omentectomy. The resected tissues revealed no malignancy. Adjuvant chemotherapy with paclitaxel and carboplatin was administered. In cases of diaphragmatic tumors, endometriosis and its associated malignancies should be considered. Laparoscopic surgery is effective in patients with such conditions.

Impact of Prior Hepatectomy History on Local Tumor Progression after Percutaneous Ablation of Colorectal Liver Metastases.

PURPOSE: To test the hypothesis that, given the current resection eligibility criteria for colorectal liver metastasis (CLM), prior hepatectomy would be associated with improved local tumor control and survival after percutaneous ablation of CLMs. MATERIALS AND METHODS: This single-institution retrospective study included 82 consecutive patients with 97 CLMs treated with ablation (radiofrequency ablation, microwave ablation, or cryoablation) from January 2005 to December 2014. Local tumor progression-free survival (LTPFS), recurrence-free survival (RFS) at any organ, and overall survival (OS) were calculated using the Kaplan-Meier method from the time of ablation and compared between patients with (n = 49) and without (n = 33) prior hepatectomy. Cox regression models were used to identify LTPFS predictors. RESULTS: Median overall follow-up period was 28 months (range, 4.5-132 months). Three-year actuarial LTPFS (patient level: 73% vs 34%, P < .001) was significantly higher in patients with than without prior hepatectomy, respectively. Similarly, 3-year RFS (23% vs 9.1%, P = .026) and OS (78% vs 48%, P = .003) were improved in patients with prior hepatectomy. At multivariate analysis, predictors of worse LTPFS were: no prior hepatectomy (hazard ratio [HR] 2.35, 95% confidence interval [CI] 1.02-5.45; P = .045), minimal ablation margin < 5 mm (HR 2.4, 95% CI 1.18-4.87; P = .016), and RAS-mutant tumor (HR 2.65, 95% CI 1.18-5.94; P = .019). CONCLUSIONS: Prior hepatectomy for CLMs is associated with improved local tumor control after percutaneous ablation of post-resection-developed CLMs.

Ablation of colorectal liver metastasis: Interaction of ablation margins and RAS mutation profiling on local tumour progression-free survival.

OBJECTIVES: To investigate effects of ablation margins on local tumour progression-free survival (LTPFS) according to RAS status in patients with colorectal liver metastases (CLM). METHODS: This two-institution retrospective study from 2005-2016 included 136 patients (91 male, median age 60 years) with 218 ablated CLM. LTPFS was performed using the Kaplan-Meier method and evaluated with the log-rank test. Uni/multivariate analyses were performed using Cox-regression models. RESULTS: Three-year LTPFS rates for CLM with minimal ablation margin ≤10 mm were significantly worse than those with >10 mm in both mutant-RAS (29% vs. 48%, p=0.038) and wild-type RAS (70% vs. 94%, p=0.039) subgroups. Three-year LTPFS rates of mutant-RAS were significantly worse than wild-type RAS in both CLM subgroups with minimal ablation margin ≤10 mm (29% vs. 70%, p<0.001) and >10 mm (48% vs. 94%, p=0.006). Predictors of worse LTPFS were ablation margins ≤10 mm (HR: 2.17, 95% CI 1.2-4.1, p=0.007), CLM size ≥2 cm (1.80, 1.1-2.8, p=0.017) and mutant-RAS (2.85, 1.7-4.6, p<0.001). CONCLUSIONS: Minimal ablation margin and RAS status interact as independent predictors of LTPFS following CLM ablation. While minimal ablation margins >10 mm should be always the procedural goal, this becomes especially critical for mutant-RAS CLM. KEY POINTS: • RAS and ablation margins are predictors of local tumour progression-free survival. • Ablation margin >10 mm, always desirable, is crucial for mutant RAS metastases. • Interventional radiologists should be aware of RAS status to optimize LTPFS.

Extended Lymphadenectomy Is Required for Incidental Gallbladder Cancer Independent of Cystic Duct Lymph Node Status.

BACKGROUND: We examined whether the incidental cystic duct nodal status predicts the status of the hepatoduodenal ligament (D1) or common hepatic artery, the pancreaticoduodenal and paraaortic lymph nodes (D2), and the overall prognosis and thus indicates whether an oncologic extended resection (OER) is required. METHODS: The study included patients who underwent OER for incidental gallbladder cancer (IGBC) during 1999-2015. Associations between a positive cystic duct node and D2 nodal status and disease-specific survival (DSS) were analyzed. RESULTS: One-hundred-eight-seven patients were included. Seventy-three patients (39%) had the incidental cystic duct node retrieved. Cystic duct node positivity was associated with positive D1 (odds ratio 5.2, p = 0.012) but not with D2. Among all patients, a positive cystic duct node was associated with worse DSS (hazard ratio [HR] 2.09). Patients without residual cancer at OER and positive incidental cystic duct node had similar DSS to patients with negative nodes 70 vs 60% (p = 0.337). Positive D1 (HR 6.07) or positive D2 (HR 13.8) was predictive of worse DSS. CONCLUSIONS: Patients with no residual cancer at OER and regional disease limited to their incidental cystic duct node have similar DSS to pN0 patients. The status of the cystic duct node only predicts the status of hepatic pedicle nodes.

Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases.

BACKGROUND: The aim of this study was to determine the prognostic value of embryonic origin in patients undergoing resection after chemotherapy for colon cancer liver metastases (CCLM). METHODS: We identified 725 patients with primary colon cancer and known RAS mutation status who underwent hepatic resection after preoperative chemotherapy for CCLM (1990 to 2015). Survival after resection of CCLM from midgut origin (n = 238) and hindgut origin (n = 487) was analyzed. Predictors of pathologic response and survival were determined. Prognostic value of embryonic origin was validated with a separate cohort of 252 patients with primary colon cancer who underwent resection of CCLM without preoperative chemotherapy. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with midgut origin tumors (RFS rate at 3 years: 15% vs 27%, P < 0.001; OS rate at 3 years: 46% vs 68%, P < 0.001). Independent factors associated with minor pathologic response were midgut embryonic origin [odds ratio (OR) 1.55, P = 0.010], absence of bevacizumab (OR 1.42, P = 0.034), and mutant RAS (OR 1.41, P = 0.043). Independent factors associated with worse OS were midgut embryonic origin [hazard ratio (HR) 2.04, P < 0.001], carcinoembryonic antigen value ≥5 ng/mL at hepatic resection (HR 1.46, P = 0.0021), synchronous CCLM (HR 1.45, P = 0.012), and mutant RAS (HR 1.43, P = 0.0040). In the validation cohort, patients with CCLM of midgut origin had a worse 3-year OS rate (55% vs 78%, P = 0.003). CONCLUSIONS: Compared with CCLM from hindgut origin, CCLM from midgut origin are associated with worse pathologic response to chemotherapy and worse survival after resection. This effect appears to be independent of RAS mutation status.

Portal Vein Embolization Reduces Postoperative Hepatic Insufficiency Associated with Postchemotherapy Hepatic Atrophy.

BACKGROUND: The risk of postoperative hepatic insufficiency (PHI) is increased among patients with significant postchemotherapy hepatic atrophy. The primary aim of this study was to evaluate whether the liver regeneration stimulated by portal vein embolization (PVE) can protect against PHI. METHODS: Clinicopathological features of 177 patients treated with preoperative chemotherapy followed by PVE and hepatectomy were reviewed. Degree of atrophy was defined as the ratio of percentage difference in total liver volume (estimated by manual volumetry) to standardized liver volume. Kinetic growth rate (KGR, degree of hypertrophy [absolute % change in future liver remnant volume] divided by the number of weeks after PVE) and PHI events were compared between patients with degree of atrophy <10 vs ≥10%. Risk factors for the PHI were assessed using logistic regression. RESULTS: Seventy patients (40%) experienced significant hepatic atrophy ≥10% following preoperative chemotherapy. PHI rates were not significantly increased in patients who experienced significant hepatic atrophy (5.6 vs 8.6%, P = 0.443). KGR <2%/week (odds ratio, 8.10, P = 0.037) was the sole independent preoperative predictor of PHI. KGR ≥2% was associated with decreased PHI in both patients with <10% atrophy (0 vs 9.5%, P = 0.035) and ≥10% atrophy (2.6 vs 16.0%, P = 0.044). CONCLUSIONS: Even in high-risk patients with ≥10% degree of atrophy from preoperative chemotherapy, KGR ≥2% mitigates the deleterious effects of hepatic atrophy and significantly reduces PHI to almost zero. In these high-risk patients, PVE with KGR calculation remains the most important preoperative technique to reduce liver failure after major hepatectomy.

Pancreatic Chymotrypsin Activity Rather Than Amylase Level Better Predicts Postoperative Pancreatic Fistula.

OBJECTIVE: To assess the predictive value of chymotrypsin activity in pancreatic juice on clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection, since pancreatic peptidases rather than glycolytic enzymes play a pivotal role in causing tissue damage due to pancreatic leakage. BACKGROUND: The risk of CR-POPF has been estimated based on amylase level in abdominal drainage fluid. METHODS: Eighty-one consecutive patients underwent pancreatoduodenectomy, and postoperative pancreatic juice and drainage fluids were collected for 14 days. The chymotrypsin activity and fluid amylase level in these fluids were measured, and their susceptibility to the elapsed postoperative time and circadian rhythm were evaluated. The predictive value for the development of CR-POPF was compared between assessment of pancreatic chymotrypsin activity versus fluid amylase level. RESULTS: No significant differences in the daily pancreatic chymotrypsin activity were observed, whereas the amylase level in pancreatic juice was susceptible to the postoperative interval and circadian rhythm. CR-POPF developed in 19 patients (23%). Assessment of pancreatic chymotrypsin activity on the first postoperative day predicted CR-POPF with a sensitivity/specificity of 84/87% (area under the curve, 0.855; cut-off value, 0.5 arbitrary units), which was better than measurement of fluid amylase level. Independent predictors of CR-POPF were the day-1 pancreatic chymotrypsin activity (≥0.5 arbitrary units, P < 0.001) and the main pancreatic duct index (<0.25, P = 0.039). CONCLUSIONS: Assessment of pancreatic chymotrypsin activity may allow for more rapid and accurate prediction of CR-POPF than use of conventional diagnostic criteria based on fluid amylase level, enabling individualized surgical procedures and postoperative drain management.

Pathologic Response to Preoperative Therapy as a Novel Prognosticator for Ampullary and Duodenal Adenocarcinoma.

BACKGROUND: The prognostic impact of pathologic response to preoperative therapy on patients with duodenal adenocarcinoma (DA) and ampullary adenocarcinoma (AMPA) has not been established. METHODS: A retrospective review of 266 patients who underwent curative resection for DA (n = 97) or AMPA (n = 169) during 1993-2015 was performed. For patients who underwent preoperative therapy, the pathologic response was systematically evaluated and classified as major (0-49% of viable residual tumor cells) or minor (≥ 50% of viable residual tumor cells). Uni- and multivariable analyses were performed to identify predictors of pathologic response and disease-specific survival (DSS). RESULTS: For the 79 patients treated with preoperative therapy (DA: n = 34; AMPA: n = 45), concomitant use of radiation (80%, 67/79) was the sole independent predictor of major pathologic response (odds ratio [OR] 8.17; 95% confidence interval [CI] 1.85-58.2; P = 0.005). The patients with major pathologic response had a better 5-year DSS rate than the patients with minor pathologic response (DA: 65 vs 25%; P = 0.028; AMPA: 85 vs 43%; P = 0.016). In the multivariable analysis of DSS for the 79 patients who underwent preoperative therapy, major pathologic response was the sole predictor of improved DSS (hazard ratio [HR] 2.88; 95% CI 1.41-5.98; P = 0.004). In the multivariable analysis of DSS for the entire cohort, pathologic stage 2 or lower was the sole predictor of better DSS. CONCLUSION: The major pathologic response to preoperative therapy predicted improved DSS after resection of DA and AMPA and might represent a new prognosticator after resection of DA and AMPA.

Individualized Treatment Sequencing Selection Contributes to Optimized Survival in Patients with Rectal Cancer and Synchronous Liver Metastases.

BACKGROUND: The optimal treatment sequence for patients with advanced rectal cancer and synchronous resectable liver metastases is controversial. We examined the outcomes associated with an individualized selection of classic, reversed, or combined approaches. METHODS: Between 1999 and 2014, 268 patients with rectal cancer and synchronous liver-only metastases underwent curative-intent multimodality therapy. Demographics and tumor and treatment details were reviewed. Survival outcomes were examined across treatment sequences and time periods (1999-2003, 2004-2008, and 2009-2014). RESULTS: Overall, 150 (56.0%) patients underwent primary tumor resection first ('classic' approach), 44 (16.4%) patients underwent simultaneous resection of the primary and liver metastases ('combined' approach), and 74 (27.6%) patients underwent liver resection first ('reversed' approach). Patients who underwent the reversed approach had more liver metastases (3 [2-5]) at presentation (vs. 1 [1-2.5] in the combined approach or 1 [1-3] in the classic approach; p < 0.001). Over time (from 1999 to 2003, to 2009 to 2014), both patients undergoing curative-intent treatment (62-122 patients) and the relative proportion of patients undergoing the reversed approach (6.4-37.7%) significantly increased. Despite higher disease burden, the 5-year overall survival (OS) was higher for patients treated in 2009-2014 versus those treated in 1999-2003 (76% vs. 45%; p < 0.002). Two hundred and ten patients (78%) were rendered free of disease; however, 58 were not due to disease progression or treatment complications, and their 5-year OS was poor at 6%. CONCLUSIONS: Individualized selection of treatment sequence based on the liver metastases and primary tumor disease burden allowed most patients to complete resection of all gross disease, and is associated with a 5-year OS rate approaching that for stage III rectal cancer in the most recent era.