Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial.

BACKGROUND: Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS: We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS: A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS: In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

Prolonged door-to-antibiotics time is associated with high hospital mortality in patients with perforated colorectal peritonitis.

PURPOSE: Colorectal perforation is a fatal disease that presents with generalized peritonitis, leading to sepsis and septic shock. Recently, the association between prolonged door-to-antibiotics time and increased mortality in sepsis has been widely reported. In this study, we investigated the prognostic impact of a prolonged door-to-antibiotics time in patients with perforated colorectal peritonitis undergoing emergency surgery. METHODS: This retrospective study included 93 patients with perforated colorectal peritonitis who underwent emergency surgery at our institution between April 2015 and August 2019. Patients were divided into two groups depending on the door-to-antibiotics time (< 162 min or ≥ 162 min). The primary outcome was in-hospital mortality. The secondary outcomes were the length of hospital stay and severe complication rate. The logistic regression analysis was used to estimate the odds ratio for in-hospital mortality. RESULTS: We identified 38 patients who presented with an extended door-to-antibiotics time (≥ 162 min) and 55 patients who presented with a shortened door-to-antibiotics time (< 162 min). We found a strong association between the door-to-antibiotics time ≥ 162 min and in-hospital mortality. There were no significant differences between the two groups regarding the length of hospital stay and postoperative complication rate. However, in multivariate analysis, extended door-to-antibiotics time was an independent prognostic factor for in-hospital mortality (odds ratio = 244; 95% confidence interval, 11 -23,885). CONCLUSION: A prolonged door-to-antibiotics time (≥ 162 min) worsened hospital mortality rates in patients with perforated colorectal peritonitis.

Survival impact of pancreatic resection for metastases in the pancreas: A retrospective multi-center study.

BACKGROUND: Pancreatic metastases from other primary malignancies are rare. There is no clear evidence for a treatment strategy for this condition. The purpose of this study was to assess the clinical outcomes, including prognostic factors for pancreatic resection of metastatic tumors in the pancreas, through a retrospective review. METHODS: Data of 35 patients who underwent pancreatic resection for pancreatic metastasis between 2005 and 2020 in eight Japanese institutions were included in this study. Survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the Cox proportional hazards model. RESULTS: The median follow-up period was 35 months (range, 5-102 months). Median duration from resection for primary tumor to resection for metastatic pancreatic tumor was 10.6 years (range, 0.6-29.2 years). The 3- and 5-year survival rates after resection for metastatic tumors in the pancreas were 89% and 69%, respectively. In contrast, the 3- and 5-year disease-free survival rates after resection for metastatic tumors in the pancreas were 48% and 21%, respectively. Performance status ≥1 at the time of resection for metastatic tumors in the pancreas (HR: 7.56, p = 0.036) and pancreatic metastasis tumor diameter >42 mm (HR: 6.39, p = 0.02) were significant poor prognostic factors only in the overall survival. CONCLUSIONS: The prognosis of pancreatic resection for metastatic tumors in the pancreas is relatively good for selected patients. However, because it is prone to recurrence after radical surgery, it should only be considered in patients with good PS.

What are the factors predictive of postoperative complications in patients with colorectal cancer undergoing stenting as a bridge to surgery?

OBJECTIVE: Using a self-expanding metal stent as a bridge to surgery (BTS) is considered a reasonable strategy for patients with acute malignant large bowel obstruction. Since postoperative complications have a negative impact on patient survival, we aim to clarify the predictors of complications in patients undergoing BTS using a self-expanding metal stent. METHODS: We conducted a retrospective review of 61 patients with colorectal cancer (CRC) who underwent stenting as a BTS at our institution. We analyzed the association of postoperative complications with clinicopathologic, surgical, and patient factors, and with the prestenting or preoperative laboratory data. RESULTS: Both postoperative complications in general and severe complications were significantly associated with a longer stenotic-section length (p = 0.007 and p = 0.003), lower preoperative hemoglobin levels (p < 0.001 and p = 0.081), and lower prestenting hemoglobin levels (p = 0.006 and p = 0.042). Multivariate logistic regression analysis showed that lower prestenting (<13.0 g/dl) and preoperative (<11.5 g/dl) hemoglobin levels were independent predictive factors for postoperative complications (odds ratio [OR]: 4.15; 95% confidence interval [CI]: 1.07-18.90; p = 0.040; and OR: 4.93; 95% CI: 1.35-20.28; p = 0.016). A stenotic-section length of 5.0 cm or greater was predictive of severe complications (OR: 25.67; 95% CI: 1.95-1185.00; p = 0.011). CONCLUSIONS: Our data suggest that lower hemoglobin levels before stenting and a longer length of the stenotic section of bowel might predict postoperative complications in patients with CRC undergoing BTS for obstruction.

Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma.

BACKGROUND: Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients. METHODS: Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated. RESULTS: CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors. CONCLUSION: Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC.

C-reactive protein level on postoperative day 3 as a predictor of anastomotic leakage after elective right-sided colectomy.

PURPOSE: To investigate the factors predictive of anastomotic leakage in patients undergoing elective right-sided colectomy. METHODS: The subjects of this retrospective study were 247 patients who underwent elective right hemicolectomy or ileocecal resection with ileocolic anastomosis between April 2012 and March 2019, at our institution. RESULTS: Anastomotic leakage occurred in 9 of the 247 patients (3.6%) and was diagnosed on median postoperative day (POD) 7 (range POD 3-12). There were no significant differences in the background factors or preoperative laboratory data between the patients with anastomotic leakage (anastomotic leakage group) and those without anastomotic leakage (no anastomotic leakage group). Open surgery was significantly more common than laparoscopic surgery (P = 0.027), and end-to-side anastomosis was less common (P = 0.025) in the anastomotic leakage group. The C-reactive protein (CRP) level in the anastomotic leakage group was higher than that in the no anastomotic leakage group on PODs 3 (P < 0.001) and 5 (P < 0.001). ROC curve analysis revealed that anastomotic leakage was significantly more frequent in patients with a serum CRP level ≥ 11.8 mg/dL [area under the curve (AUC) 0.83]. CONCLUSION: A serum CRP level ≥ 11.8 mg/dL on POD 3 was predictive of anastomotic leakage being detected on median POD 7.

[Safety of Pancreaticoduodenectomy in Patients of Advanced Age and Our Efforts to Prevent Postoperative Pneumonia].

With the aging of society, surgical patients are becoming older. The same trend can be seen in patients undergoing highly invasive operations, such as pancreaticoduodenectomy(PD). The risk of postoperative complications is reportedly higher in patients of advanced age, and postoperative pneumonia occurs at particularly high frequency. We investigated the safety of PD in patients of advanced age with a focus on the prevention of postoperative pneumonia. In total, 223 patients underwent PD at our department from January 2015 to December 2020. We compared various parameters between older patients(≥80 years of age, n=32)and younger patients(<80 years of age, n=191). Although older patients had lower nutrition scores, there was no significant difference in the incidence of postoperative complications between the two groups. Three older patients who were undergoing swallowing rehabilitation by a speech-language therapist did not develop postoperative pneumonia. However, one patient who did not receive swallowing rehabilitation developed postoperative pneumonia. Based on these findings, we plan to incorporate swallowing evaluation before postoperative oral intake into the clinical pathway and introduce speech-language therapy intervention in patients of advanced age.

Predictive model for postoperative pleural effusion after hepatectomy.

AIM: Severe postoperative pleural effusion (sPOPE) after hepatectomy can lead to respiratory distress and may require thoracic drainage, leading to prolonged hospitalization. Preventive chest tube insertion may be useful for patients at high risk for sPOPE. We aimed to develop a predictive model for sPOPE after hepatectomy and evaluate indications for preventive chest tube insertion using our model. METHODS: We evaluated all patients who underwent hepatectomy from 2013 to 2020. Risk factors for sPOPE were used to develop a predictive model for sPOPE, which was validated in a cohort that received preventative chest tube placement postoperatively. RESULTS: A total of 325 patients were analyzed. Thirty-one (9.5%) patients had a preventive chest tube placed at the end of their operation. Twenty-one patients out of the remaining 294 patients developed sPOPE. Multivariate analysis identified resection containing segment 8 [relative risk (RR) 3.24, P = .022], intraoperative bleeding ≥ 500 g (RR 4.02, P = .008), intraoperative diaphragmatic incision (RR 6.96, P = .042) and open hepatectomy (RR 7.51, P = .016) as independently associated with sPOPE. The estimated probability of sPOPE ranged from 0.4% in patients with none of these factors to 73.4% in the presence of all factors. Among the 31 patients who received a preventive chest tube, more patients in the high-risk group defined by the model had postoperative pleural effusions compared to the low-risk group (P = .012). CONCLUSION: Our predictive model for sPOPE using four risk factors allows for reliable prediction and may be useful for selection of preventive chest tube in patients undergoing hepatectomy.

How to treat remnant cholecystitis after subtotal cholecystectomy: two case reports.

BACKGROUND: Subtotal cholecystectomy in patients with severe acute cholecystitis is considered a "bailout" option when the safety of the bile duct cannot be guaranteed. However, subtotal cholecystectomy has a long-term risk of remnant cholecystitis. The appropriate management of remnant cholecystitis has not been fully elucidated. CASE PRESENTATION: Case 1 was a 66-year-old man who had undergone subtotal cholecystectomy 14 years prior to the development of remnant cholecystitis. We first performed endoscopic gallbladder drainage to minimize inflammation, and then proceeded with elective surgery. We performed a reconstituting procedure for the residual gallbladder due to significant adhesions between the cystic and common bile ducts. Case 2 was a 56-year-old man who had undergone subtotal cholecystectomy for abscess-forming perforated cholecystitis 2 years prior to the development of remnant cholecystitis. He underwent endoscopic drainage followed by complete remnant cholecystectomy 4 months later. CONCLUSION: Endoscopic gallbladder drainage is a useful strategy to improve inflammation and reduce the risk of bile duct injury during remnant cholecystectomy.

Rupture of a huge infectious abdominal chronic expanding hematoma.

A 72-year-old woman was referred to our hospital with the diagnosis of peritonitis due to the rupture of a huge abdominal cystic tumor, 27 cm in diameter. Abdominal computed tomography 14 years before revealed the tumor, which was 18 cm in diameter. She had undergone no examinations or treatment in the interim. She was in shock upon presentation to our hospital. She was intubated immediately and underwent an emergent laparotomy. The huge ruptured tumor with adherent small intestine was resected. The tumor weighed 6 kg and consisted of solid and cystic components filled with 4 kg of brown feces-like fluid. Bacteroides fragilis was detected in a fluid specimen. The cystic component of the tumor was filled with old blood clots, and a portion of the tumor wall was highly calcified. Old blood and fibrin with blood vessels of various sizes inside the tumor were observed during the pathologic evaluation; there were no malignant features. The final pathologic diagnosis was a chronic expanding hematoma (CEH). The patient had an uneventful recovery and was discharged 16 days post-operatively. She was involved in a traffic accident approximately 30 years before the current hospital admission; however, she did not recall if she had abdominal pain at that time. A CEH is a benign lesion, but rupture of a CEH can be life-threatening.

Efficacy of delayed primary closure with intrawound continuous negative pressure and irrigation treatment after surgery for colorectal perforation.

AIM: Surgical-site infections (SSIs) often occur after surgery for colorectal perforation. We introduced delayed primary closure (DPC) after intrawound continuous negative pressure and irrigation treatment (IW-CONPIT) to prevent SSIs. We aimed to evaluate the efficacy of DPC after IW-CONPIT compared with primary closure (PC) after surgery for colorectal perforation. METHODS: We undertook a retrospective study including 22 patients who underwent DPC (DPC group) and 18 patients who underwent PC (PC group) at our hospital between April 2015 and January 2017. The primary outcome was the SSI rate. The secondary outcomes were other complications (<30 days), length of hospital stay, and costs. RESULTS: The SSI rate was significantly lower in the DPC group than in the PC group (40% vs. 94%, P = 0.0006). Moreover, superficial and deep incisional SSIs, infectious complications, and Clavien-Dindo classification grade ≥ 2 complications were also significantly diminished in the DPC group. Conversely, the length of hospital stay and costs were not significantly different between the two groups. Multivariate analyses revealed that the significant independent protective factor against SSI after surgery for colorectal perforation was DPC after IW-CONPIT (odds ratio 0.04; 95% confidence interval, 0.002-0.25). CONCLUSION: Delayed primary closure after IW-CONPIT reduced SSIs after surgery for colorectal perforation compared with PC.

Varied application of intercostal trans-diaphragmatic ports for laparoscopic hepatectomy.

BACKGROUND: The ribcage and diaphragm are mechanical barriers for laparoscopic access during hepatectomy. Here, we introduce the varied application of intercostal trans-diaphragmatic ports during laparoscopic hepatectomy, and describe the management of intercostal ports with key technical points. METHODS: From January 2013 to December 2017, 180 patients underwent laparoscopic hepatectomy. In 32 of these patients (17.8%), intercostal ports (31 right and one left) were applied, and we analyzed the feasibility and safety of intercostal ports during laparoscopic hepatectomy. RESULTS: The main tumor location was segment VII and VIII (78%). The major type of laparoscopic hepatectomy was partial hepatectomy (91%). In the majority of cases (66%) the number and size of intercostal trocars was a single 5-mm port. The median operative time and blood loss were 232 min and 50 mL, respectively. A chest drain was placed via the hole of the intercostal port on the chest wall in two cases (6.3%). The median duration of the post-operative hospital stay was 6 days. There was no conversion, and a pure laparoscopic hepatectomy was achieved in all cases. There was no mortality. As for complications due to the application of intercostal ports, an asymptomatic pneumothorax was detected in only one case, and it was cured by conservative treatment. CONCLUSIONS: The ribcage and diaphragm could be overcome as barriers to laparoscopic access by the placement of intercostal ports with minimal access during laparoscopic hepatectomy. The use of an intercostal port and proper management allows for a feasible approach and safe resection during laparoscopic hepatectomy.

[Perforated Marginal Ulcer after Subtotal Stomach Preserving Pancreaticoduodenectomy-Report of Five Cases].

PURPOSE: Perforated marginal ulcer after pancreaticoduodenectomy(PD)is a delayed complication. We evaluated the characteristics of the patients presenting perforated marginal ulcer after PD. METHODS: Five cases of perforated marginal ulcer after PD were reported at our hospital between 2008 and 2018, and the characteristics of these patients were evaluated. RESULTS: All 5 patients(4 females)with median age 73 years underwent subtotal stomach-preserving PD(SSPPD). In spite of the administration of gastric antisecretory medication, perforated marginal ulcer occurred in 3 patients(60%). All patients were treated with direct suture and omentum patch, and no mortality was reported. CONCLUSIONS: The perforating marginal ulcer after SSPPD occurred despite the administration of the gastric antisecretory medication. Treatment with direct suture and omentum patch was effective in perforated marginal ulcer after SSPPD.

[Primary Small Intestinal Cancer-A Clinicopathological Study of Seven Cases].

The clinicopathological features of primarysmall intestinal cancer were assessed retrospectively. Seven patients underwent resection of small bowel cancer in our hospital between June 2011 and January 2019. The mean age of the patients was 62.9 years, and the male to female ratio was 4:3. Five patients were symptomatic, and the correct preoperative diagnosis rate was 28.6%. The average tumor diameter was 5.3 cm, and the median resected intestine length was 25 cm. Histopathological examination revealed that there were 2 patients with poorlydifferentiated tumors and 3 patients with pStage ⅡA, 3 with pStage ⅡB, and 1 with pStage ⅢA disease. Recurrence after surgeryoccurred in 4 patients, including local recurrence in 2 patients and lymph node recurrence in 1 patient. Median survival was 24.5 months. The resected intestinal length was longer and the mesenteric arterydissection was more extensive in survivors than in dead patients. In contrast, the dead patients were older than the survivors and had undifferentiated tumor, ly2/ly3, lymph node metastasis, and recurrence. Moreover, recur- rence occurred in 4 patients who had lymph node metastasis, and/or undifferentiated tumor type, and/or ly2/ly3. An adequate intestinal excision margin along with mesenteric lymph node dissection might be required to improve the survival of patients with primaryintestinal cancer.

Frailty Predicts Severe Postoperative Complication after Elective Hepatic Resection.

BACKGROUND: Frail patients are likely to suffer from postoperative complication, but this assumption has not been well confirmed. OBJECTIVES: This study aims to clarify the importance of frailty in patients undergoing hepatectomy for predicting severe postoperative complications. METHOD: One hundred and forty-three patients aged >65 years undergoing hepatectomy between 2011 and 2016 were enrolled in this study. The relevance of frailty versus sarcopenia for postoperative outcome was assessed. We defined clinical frailty (CF) as a CF scale >4. Sarcopenia was defined by the total muscle area at the level of the third lumbar vertebra measured on computed tomography. RESULTS: There were 16 patients (11%) with CF and 80 patients (56%) with sarcopenia. CF was associated with high age (p < 0.0001), severe postoperative complications (Clavien-Dindo classification ≥3) (p = 0.0059), and postoperative in-hospital stay (p = 0.0013). On the other hand, sarcopenia was not associated with postoperative outcome. Logistic regression analysis revealed that only CF was an independent predictor of severe postoperative complication (risk ratio of 4.2; p = 0.017). The occurrence of organ/space surgical site infection was significantly higher in the frailty group than in the non-frailty group. CONCLUSION: CF, but not sarcopenia, is a robust predictor of severe postoperative complications for patients undergoing hepatectomy.

Conversion surgery for initially unresectable pancreatic ductal adenocarcinoma with synchronous liver metastasis after treatment with FOLFIRINOX.

FOLFIRINOX is a highly effective anticancer treatment, even in advanced pancreatic cancer, which provides a potential cure in patients initially treated with a palliative strategy. A 47-year-old man was found to have an unresectable pancreatic cancer (4 cm in size) surrounding both the superior mesenteric artery and superior mesenteric vein. A simultaneous liver metastasis in Segment 8, with a diameter of 17 mm, was also detected. The pancreatic tumor markers CEA, CA19-9, and DUPAN-2 were significantly elevated to 21.7 ng/mL, 6224 ng/mL, and 1200U/mL, respectively. After 21 courses of FOLFIRINOX, the primary pancreatic tumor diminished in size (partial response) from 42 to 17 mm, and the liver mass almost disappeared. The tumor markers significantly decreased to almost normal levels. Fourteen months after the initial chemotherapy, conversion surgery was performed. Upon surgical resection, the pancreatic tumor was found to be Grade 1b, and a pathologically complete response was observed for the liver metastasis. The patient is still alive 32 months after initial treatment with no recurrence. This is an informative case of a locally advanced pancreatic cancer with a synchronous liver metastasis that had a significant response to FOLFIRINOX, allowing for subsequent curative resection.

The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors.

BACKGROUND: Few reliable prognostic markers have been established despite elucidation of the molecular mechanisms of gastrointestinal stromal tumor (GIST) development. We evaluated F-box and WD repeat domain-containing 7 (FBXW7), a cell-cycle-regulating and tumor suppressor, in GISTs. We aimed to determine the clinical relevance of FBXW7 in GISTs and characterize the molecular mechanism of FBXW7 in a GIST cell line. METHODS: We measured FBXW7 expression in 182 GIST cases, correlated the expression levels with clinicopathological features, and characterized the molecular mechanism underlying suppressed FBXW7 expression in GIST cells in vitro. RESULTS: Of the 182 GISTs, 98 (53.8%) and 84 (46.2%) were categorized in the high and low FBXW7 expression groups, respectively. Compared with the high FBXW7 expression group, the low expression group showed a significantly poorer prognosis in terms of recurrence-free (P = 0.01) and overall (P = 0.03) survival. FBXW7 expression was a significant independent factor affecting the 10-year recurrence-free survival rate (P = 0.04). In vitro, FBXW7-specific siRNAs enhanced c-myc and Notch 1 protein expression and upregulated cell proliferation, invasion, and migration. CONCLUSION: FBXW7 is a potential predictive marker of recurrence after curative resection of GISTs. FBXW7 expression may help identify patients benefitting from adjuvant therapy more precisely compared with a conventional risk stratification model.

Frailty predicts severe postoperative complications after elective colorectal surgery.

BACKGROUND: We aim to clarify if frailty affects severe postoperative complications in elective colorectal surgery. METHODS: Consecutive 269 colorectal cancer patients older than 65 years undergoing curative surgery were enrolled in this study. The relevance of the frailty and sarcopenia to postoperative outcome was assessed. Clinical frailty (CF) was defined as clinical frailty scale (CFS) ≥ 4. Sarcopenia was assessed by measuring skeletal muscle area using computed tomography. RESULTS: Seventy-eight patients (29%) had CF and 159 patients (59%) had sarcopenia. CF was significantly associated with older age (P = 0.0008), postoperative severe complications (P = 0.001), and postoperative in-hospital stay (P < 0.0001), although sarcopenia was not. Logistic regression analysis revealed that low anterior resection and CF were independent predictors of severe postoperative complications (P = 0.038 and P = 0.001, respectively). CONCLUSION: CF, but not sarcopenia, is a robust predictor of severe postoperative complications in patients with colorectal cancer.