Surgical site infection after laparoscopic resection of colorectal cancer is associated with compromised long-term oncological outcome.

BACKGROUND: We evaluated the influence of infectious complications, particularly surgical site infection (SSI), on long-term oncological results after elective laparoscopic resection of colorectal cancer. METHODS: A total of 199 patients who underwent laparoscopic elective resection with negative resection margins for stage I-III colorectal cancer were retrospectively examined. The postoperative course was recorded based on hospital records, and cancer relapse was diagnosed based on radiological or pathological findings under a standardized follow-up program. The severity of complications was graded using Clavien-Dindo (CD) classification. RESULTS: SSI was found in 25 patients (12.6%), with 12 (6.0%) showing anastomotic leak. The postoperative relapse-free survival (RFS) rate was significantly lower in patients with SSI (49.2%) than in patients without SSI (87.2%, P<0.001). Differences in RFS were found after both colectomy and rectal resection (P<0.001 and P<0.001, respectively). RFS did not differ between patients who had major SSI CD (grade III) and those who had minor SSI CD (grades I or II). Multivariate Cox regression analysis identified the occurrence of SSI and pathological stage as independent co-factors for RFS (P<0.001 and P=0.003). CONCLUSION: These results suggest that postoperative SSI compromises long-term oncological results after laparoscopic colorectal resection. Further improvements in surgical technique and refinements in perioperative care may improve long-term oncological results.

Accuracy of Modern Clinical Risk Score Including RAS Status Changes Based on Whether Patients Received Perioperative Chemotherapy for Colorectal Liver Metastases.

BACKGROUND: A modified Fong clinical score (m-Fong CS) that includes the RAS mutation status has recently been proposed and offered an improved survival stratification of patients who undergo surgery and systemic chemotherapy for colorectal liver metastases (CLM). The aim of this study is to assess whether a CS that includes RAS status is influenced by whether patients receive perioperative chemotherapy. METHODS: We created a new CS using multivariate analysis of data of patients who underwent hepatectomy for CLM for the first time between 2010 and 2016 at a single hospital (n = 341, 79% received perioperative chemotherapy). The resulting CS and m-Fong CS were then validated in the patient cohort at three other hospitals (n = 309). Furthermore, the applicability of the two CS in the total cohort (n = 650) was tested according to whether the patients received perioperative chemotherapy. RESULTS: The new CS comprised mutant RAS status, ≥4 CLMs, and a CA19-9 level ≥100 U/mL (1 point per factor). Both the new CS and m-Fong CS failed to stratify the survival of the 309 patients in the validation cohort, including those who did not receive perioperative chemotherapy (29%). Both of the CS accurately stratified the survival of patients who underwent perioperative chemotherapy but not of those who underwent surgery alone. CONCLUSION: A CS that includes the RAS mutation status can stratify the survival of patients who undergo hepatectomy combined with perioperative chemotherapy, but it has limited value for patients who undergo surgery alone.

Early detection of infectious complications using C-reactive protein and the procalcitonin levels after laparoscopic colorectal resection: a prospective cohort study.

PURPOSE: The predictive values of the C-reactive protein (CRP) and procalcitonin (PCT) levels for postoperative infectious complications were investigated in patients who underwent elective laparoscopic resection of colorectal cancer. METHODS: A total of 154 consecutive patients who underwent elective laparoscopic resection for colorectal cancer (CRC) were prospectively studied. The CRP and PCT levels on the first postoperative day (POD1) and the fourth postoperative day (POD4) were measured. Any correlations between the CRP and PCT levels on POD1 and POD4 with the occurrence of infectious complications were examined. RESULTS: Infectious complications occurred in 18 (11.7%) patients. CRP on POD1 and CRP and PCT on POD4 were significantly higher in patients who developed infectious complications than in those who did not. The areas under the receiver operating characteristic curves of CRP on POD1 and CRP and PCT on POD4 were 0.597, 0.763 and 0.768, respectively. The cut-off values of CRP and PCT levels on POD4 were 14.33 mg/dl and 0,264 ng/ml, respectively. Whereas the positive predictive value of an elevated CRP level was high, the negative predictive value of an elevated PCT was high. CONCLUSION: The CRP and PCT levels on POD4 are both considered to be useful for the early detection of infectious complications after laparoscopic resection of CRC.

Prognostic Impact of Budding Grade in Patients With Residual Liver Recurrence of Colorectal Cancer After Initial Hepatectomy.

BACKGROUND: Many patients undergoing hepatectomy for colorectal liver metastases (CRLM) experience recurrence. However, no criteria for screening candidates to undergo repeat hepatectomy (RH) for CRLM have been established. Budding, one form by which colorectal carcinoma malignancies are expressed, is a new pathologic index. This study aimed to analyze prognostic factors, including budding, and to provide criteria for screening candidates to undergo RH for recurrent CRLM. METHODS: Data of 186 consecutive patients who underwent hepatectomy for CRLM between April 2008 and December 2015 were collected. Survival was calculated using the Kaplan-Meier method. Uni- and multivariate analyses were performed to determine factors significantly affecting mortality. RESULTS: Of 186 patients, 131 experienced recurrence after hepatectomy, with 83 of the 131 patients showing recurrence in the liver, and 52 of these 83 patients undergoing primary surgery at the authors' institution and having information on budding grade. In the univariate analysis, preoperative chemotherapy, budding grade, extrahepatic metastases, and number of liver metastases at the time of recurrence were associated with overall survival (OS) for the 52 patients. In the multivariate analysis, budding grade and number of liver metastases at the time of recurrence were associated with OS. CONCLUSION: The study examined simple prognostic factors that could help to screen patients better for RH. Repeat hepatectomy improved the prognosis for patients with recurrent CRLM. The independent prognostic factors for OS were number of liver metastases at recurrence as a conventional factor and budding grade as a new pathologic factor. With budding used as an index, patients who could benefit from hepatectomy can be screened more precisely.

Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer.

BACKGROUND: Fibrosis surrounding cancer cells has been shown to affect cancer cell metastatic behavior. The present study aimed to explore the utility of myxoid stroma as a predictive factor for postoperative relapse in patients with stage II colon cancer. METHODS: The present study retrospectively investigated 169 patients who underwent curative surgical resection of stage II colon cancer. The fibrotic stroma was classified according to Ueno's criteria, and the patients were divided into the myxoid (MY) group and the non-MY (NMY) group. We also recorded tumor budding (TB) and investigated the combination of MY and TB for postoperative relapse. Postoperative survival was also explored. RESULTS: Thirty-two (18.9%) patients had MY. MY was significantly associated with tumor budding (TB) and postoperative relapse (p <  0.001 and p <  0.001, respectively). The 5-year RFS rates in MY group and NMY group were 52.1 and 94.6% (p < 0.0001), and the 5-year OS rates in MY group and NMY group were 74.6 and 93.3% (p = 0.001). Multivariate analysis showed that both MY and TB were significant risk factors for postoperative relapse (p < 0.001 and p = 0.02, respectively), and that only TB was a significant risk factor for OS (p = 0.043). Furthermore, compared with patients with either one of MY or TB, patients with both MY and TB had postoperative relapse more frequently (11.4% vs. 53.8%). CONCLUSIONS: The present study suggests that MY is a predictive marker for postoperative relapse in patients with stage II colon cancer.

Stapler sizes optimized for pancreatic thickness can reduce pancreatic fistula incidence after distal pancreatectomy.

PURPOSE: The purpose of this paper was to identify the optimum-sized stapler cartridges for reducing the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: The authors retrospectively analyzed 101 patients who underwent DP with a triple-row stapler to identify the clinicopathological factors that strongly influence POPF after DP. The height difference (HD) was defined as the difference between the pancreatic thickness and the height of the closed stapler. RESULTS: POPF occurred in 58 (57%) patients. A multivariate analysis identified HD and pancreatic thickness as independent risk factors for the occurrence of POPF after DP. Akaike's information criterion for identifying the risk factors was more favorable for HD (115.18) than for pancreatic thickness (118.02). The incidence of POPF was significantly lower (29%) in patients with an HD between 6 and 12 mm than in the other two groups (< 6-mm group: 100%, P = 0.008; ≥ 12-mm group: 84%, P < 0.001). CONCLUSIONS: A too-thick or too-narrow pancreas carries a risk of developing POPF after DP when using a triple-row stapler. Selecting staplers to achieve an HD of 6-12 mm may reduce the incidence of POPF following DP.

Laparoscopic fenestration for a large ruptured splenic cyst combined with an elevated serum carbohydrate antigen 19-9 level: a case report.

BACKGROUND: Non-parasitic splenic cysts are associated with elevated serum carbohydrate antigen (CA) 19-9 levels. We report a case in which a 23-year-old female exhibited a large ruptured splenic cyst and an elevated serum CA19-9 level. CASE PRESENTATION: The patient, who experienced postprandial abdominal pain and vomiting, was transferred to our hospital and was found to have a large splenic cyst during an abdominal computed tomography (CT) scan. On physical examination, her vital signs were stable, and she demonstrated rebound tenderness in the epigastric region. An abdominal CT scan revealed abdominal fluid and a low-density region (12 × 12 × 8 cm) with enhanced margins in the spleen. The patient's serum levels of CA19-9 and CA125 were elevated to 17,580 U/mL and 909 U/mL, respectively. A cytological examination of the ascitic fluid resulted in it being categorized as class II. Finally, we made a diagnosis of a ruptured splenic epidermoid cyst and performed laparoscopic splenic fenestration. The patient's postoperative course was uneventful, and she was discharged on postoperative day 5. The cystic lesion was histopathologically diagnosed as a true cyst, and the epithelial cells were positive for CA19-9. Follow-up laboratory tests performed at 4 postoperative months showed normal CA19-9 (24.6 U/L) and CA125 (26.8 U/L) levels. No recurrence of the splenic cyst was detected during the 6 months after surgery. CONCLUSION: Laparoscopic fenestration of a ruptured splenic cyst was performed to preserve the spleen, after the results of abdominal fluid cytology and MRI were negative for malignancy.

The impact of postoperative adjuvant chemotherapy on the development of nonalcoholic fatty liver disease after pancreatoduodenectomy.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) after pancreatoduodenectomy (PD) is increasingly being recognized as a late postoperative complication, but the main causes have not been fully investigated. This study aimed to clarify the relationship between NAFLD after PD and postoperative adjuvant chemotherapy, focusing particularly on the adjuvant chemotherapy regimens administered. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 154 patients who underwent PD from April 2007 to December 2013, to identify the clinicopathologic factors most strongly influencing NAFLD development after PD. Moreover, the postoperative adjuvant chemotherapeutic regimen and the course after the cessation of adjuvant chemotherapy were examined in detail. RESULTS: The incidence of postoperative NAFLD was 26.6% (41/154). The incidence of NAFLD was significantly higher in the patients with than in those without adjuvant chemotherapy: 38% versus 19% (P = 0.016). Multivariate analysis identified postoperative adjuvant chemotherapy (P = 0.021) and remnant pancreatic volume (P < 0.0001) as independent risk factors. The prevalence of NAFLD after PD was higher in patients treated with the S-1 regimen than in those given either regimens such as those containing gemcitabine or no adjuvant chemotherapy. Recovery from NAFLD 1 y after the cessation of adjuvant chemotherapy was observed in 54.5% (12/22) of patients receiving this treatment. In those treated with the S-1 regimen, improvement was more frequent than in those not receiving adjuvant chemotherapy (57.1% versus 11.8%, P = 0.018). CONCLUSIONS: Considering the development of NAFLD, adjuvant chemotherapy after PD should be cared for the patients with small remnant pancreas.

Incisional surgical site infections by subcutaneous soaking of wound with aqueous 0.05% chlorhexidine gluconate in gastroenterological surgery: A randomized controlled trial.

BACKGROUND: Chlorhexidine gluconate solution is superior to povidone-iodine for prevention of surgical site infection. However, the overall efficacy of chlorhexidine gluconate for surgical site infection prevention in various types of gastroenterological surgery, as well as the optimal concentration of chlorhexidine gluconate, remain unclear. The aim of the present study was to clarify whether subcutaneous wound soaking with chlorhexidine gluconate would reduce the incidence of surgical site infection associated with gastroenterological surgery in patients with wound classes Ⅱ to Ⅳ. METHODS: Patients were randomly assigned (1:1) to either wound soaking with chlorhexidine gluconate (chlorhexidine gluconate group) or no chlorhexidine gluconate soaking (control group). After closure of the abdominal fascia, gentle subcutaneous soaking of the wound was performed using gauze fully soaked in aqueous 0.05% chlorhexidine gluconate before skin closure. Incisional surgical site infection was diagnosed using the Centers for Disease Control and Prevention criteria. The primary end point was the occurrence of incisional surgical site infection. RESULTS: Among 363 patients, 245 (67%) underwent laparoscopic surgery. All 363 patients were included-181 in the chlorhexidine gluconate group (49.9%) and 182 (50.1%) in the control group. There were no significant inter-group differences in patient background, the type of procedure, or wound classification. The incidence proportion of incisional surgical site infection was significantly lower in the chlorhexidine gluconate group than in the control group (9.4% vs 19.2%; P = .008). CONCLUSION: Subcutaneous wound soaking with chlorhexidine gluconate reduces the incidence of incisional surgical site infection in patients undergoing gastroenterological surgery.

A Case of a Grade 3 Gallbladder Neuroendocrine Tumor With Rapid Recurrence After Curative Resection.

Primary gallbladder neuroendocrine tumor (GB-NET) is extremely rare. Therefore, tumor behavior and adequate treatment in GB-NETs are still unclear. A 74-year-old man without any specific complaints was referred to our hospital cause of gallbladder tumor. Abdominal ultrasonography examination revealed a 22-mm non-pedunculated tumor in the gallbladder body. Contrast-enhanced computed tomography showed a polyp that was enhanced in the arterial phase. The patient underwent gallbladder bed resection and radical lymphadenectomy with a diagnosis of gallbladder carcinoma. Macroscopically, the resected specimen showed a nodular expanding tumor measuring 32×15 mm in the gallbladder body. From the pathological findings, a grade 3 GB-NET was diagnosed. Only cystic lymph node metastasis was observed. The patient was discharged uneventfully, but bone and lymph node metastasis were detected eight months after surgery. We conclude that grade 3 GB-NET shows occasionally malignant biological behavior although NET G3 is distinguished from neuroendocrine carcinoma in the current WHO 2019 classification of NET.

Novel Clean End-to-End Anastomosis Method, Without Opening the Stomach Lumen, in Totally Laparoscopic or Robotic Pylorus-Preserving Gastrectomy.

PURPOSE: Intra-abdominal infection is a common postoperative complication of laparoscopic pylorus-preserving gastrectomies (PPGs). Many studies have reported that intra-abdominal infectious complications after gastrectomy adversely affect patient survival outcomes. To prevent gastric fluid leakage into the abdominal cavity, we developed a novel anastomosis method in which the stomach lumen is not opened (termed the non-opened clean end-to-end anastomosis method [NoCEAM]) and evaluated its feasibility. MATERIALS AND METHODS: Subsequent to lymphadenectomy, the oral and anal resection lines were sutured using an intraoperative endoscope. After closing the stomach circumferentially with clips, the specimen was rolled outward like a "donut." We resected the specimen circumferentially using a linear stapler, and anastomosis was completed simultaneously. We examined the feasibility of this procedure ex vivo, using three porcine stomachs, and in vivo, using one pig. Subsequently, we applied the procedure to 13 consecutive patients with middle-third early gastric cancer utilizing laparotomic, laparoscopic, and robotic PPG. RESULTS: NoCEAM was completed in all porcine models and human cases. In the human cases, the mean operation time (±standard deviation) was 279±51 minutes, and mean blood loss volume was 22±45 mL. The mean number of linear staples used was 5.06±0.76. None of the patients had complications, and all were discharged on the eighth postoperative. The serum total protein, serum albumin, and hemoglobin levels did not change significantly after surgery. CONCLUSIONS: NoCEAM is feasible and safe for performing totally laparoscopic or robotic PPG. It may reduce postoperative complications, such as intra-abdominal infections.

Primary hepatic neuroendocrine neoplasm presenting as a massive cystic liver tumor mimicking mucinous cystic neoplasm of the liver: A case report and literature review.

Neuroendocrine neoplasms (NENs) preferentially arise in the bronchopulmonary tree or the gastrointestinal tract. Notably, primary hepatic NENs are extremely rare. The present study describes a case of hepatic NEN presenting as a giant hepatic cystic lesion. A 42-year-old woman presented with a large liver tumor. Contrast-enhanced abdominal computed tomography revealed a cystic tumor (18 cm) in their left liver. The tumor exhibited liquid components and mural solid nodules with enhanced effects. The lesion was diagnosed as mucinous cystic carcinoma (MCC) preoperatively. The patient underwent a left hepatectomy, and the postoperative course was uneventful. The patient has been alive without recurrence for 36 months postoperatively. The pathological diagnosis was NEN G2. This patient had ectopic pancreatic tissue in the liver and thus the ectopic pancreatic origin of the tumor was suspected. The present study describes a case of resected cystic primary NEN of the liver that was difficult to differentiate from mucinous cystic neoplasms. As primary liver NENs are extremely rare, further studies are needed to establish their diagnosis and treatment.

Metastasis to the skin at the drain site after complete resection of the lower bile duct cancer: report of a case.

There are extremely few reports of metastases from a lower cholangiocarcinoma to the skin except for metastatic seeding in a percutaneous transhepatic biliary drainage catheter tract. This report presents a rare case of metastases to the skin after the removal of a drain following curative pancreaticoduodenectomy for lower bile duct cancer (LBDC). A 73-year-old female had undergone subtotal stomach-preserving pancreaticoduodenectomy. Skin metastasis was noted at the site where the drain from the lower border at pancreaticojejunostomy had been removed 22 weeks postoperatively, and it was en bloc resected with the abdominal wall without exposing the carcinoma. Multiple nodules were confirmed in the axilla and chest wall 40 weeks after the initial operation. Careful discussion is necessary to avoid this mode of metastasis. The surgical field should not be exposed to pancreatic juice, even with LBDC. Nevertheless, this case is rare. Therefore, the risks and benefits of using such drains must be considered.

Tumor Budding as a Predictive Marker of Relapse and Survival in Patients With Stage II Colon Cancer.

BACKGROUND/AIM: Tumor budding (TB) has recently been recognized worldwide as a prognostic predictor in several solid cancers. The objective of this study was to explore the relationship between TB and clinicopathological characteristics, postoperative relapse, and survival in patients with stage II colon cancer. PATIENTS AND METHODS: A total of 213 patients with stage II colon cancer were retrospectively enrolled at Saitama Medical Center, Dokkyo Medical University from 2010 to 2016. TB was evaluated in hotspot areas on hematoxylin and eosin-stained slides at the invasive front of the tumor to define a low-grade group (BD1) and a high-grade group (BD2 or BD3). RESULTS: High-grade TB was found in 38.3% of cases, and was associated with pT4, presence of lymphovascular invasion, and tumor relapse (p=0.02, p=0.03, p=0.002, respectively). Patients with highgrade TB showed worse relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB (5-year RFS: High 75.6% vs. Low 92.1%, p=0.001; 5-year OS: High 93.7% vs. Low 93.7%, p=0.001). On multivariate analysis for predictors of RFS and OS, high-grade TB was significant for both RFS and OS (RFS, p=0.003; OS, p=0.005). Patients with high-grade TB experienced lung and liver relapses significantly more frequently than patients with low-grade TB (p=0.03 each). Among patients who received adjuvant chemotherapy (AC), no patients showed lung or liver relapse even in the presence of high-grade TB. CONCLUSION: TB may offer a useful predictor of relapse in patients with stage II colon cancer after surgery, and AC should be considered for patients with high-grade TB.

Comparison of postoperative plasma D-dimer levels between patients undergoing laparoscopic resection and conventional open resection for colorectal cancer.

INTRODUCTION: D-dimer is widely used in clinical pretests for venous thromboembolism exclusion, and its elevation suggests the presence of thrombus. The extent of hypercoagulability after colorectal surgery has not been systematically compared between patients who have undergone laparoscopic surgery and open surgery. The present study measured D-dimer levels sequentially in patients undergoing colorectal surgery and compared the extent of hypercoagulability between laparoscopic surgery and open surgery. METHODS: A prospective cohort study involving 169 patients who underwent resection of colorectal cancer at Saitama Medical Center, Dokkyo Medical University, was conducted between January 2013 and September 2014. To measure D-dimer level, peripheral blood was obtained on postoperative day (POD) 1, POD4, and POD7. Enoxaparin sodium was administered twice daily as the routine prophylactic anticoagulant therapy on POD2 to 7. RESULTS: D-dimer levels on POD1, POD4, and POD7 were significantly higher after open surgery than after laparoscopic surgery. Older age, pathologically advanced stage cancer, greater intraoperative blood loss and higher preoperative D-dimer levels were significantly associated with higher D-dimer levels on POD1, POD4, and POD7. Patients who completed the course of postoperative enoxaparin injections had significantly lower D-dimer levels on POD7 than those who did not receive postoperative enoxaparin injections. Multiple regression analyses of postoperative D-dimer level showed that laparoscopic surgery was a significant and independent factor affecting D-dimer level on POD4 and POD7. CONCLUSION: This study showed that postoperative D-dimer levels were lower after laparoscopic surgery than after open surgery. The limited invasiveness of laparoscopic surgery may be beneficial to reduce the risk of postoperative deep vein thrombosis.

A patient with a pancreatic neuroendocrine tumor and multiple liver metastases achieved a long-term partial response to third-line streptozocin treatment.

The Japanese guideline for gastroenteropancreatic neuroendocrine tumor treatment recommends everolimus or sunitinib as first-line treatment for unresectable pancreatic neuroendocrine tumors (PNETs). Streptozocin (STZ) is recommended as an alternative. We encountered a patient with PNET who had multiple liver metastases and who showed a remarkable response to third-line STZ. The patient was a 50-year-old man with a pancreatic head tumor 32 mm in diameter. We planned to perform subtotal stomach-preserving pancreaticoduodenectomy, but abandoned resecting the pancreas during the surgery upon discovering a small liver tumor 3 mm in diameter, examination of frozen sections of which revealed a poorly differentiated adenocarcinoma. However, the final pathological examination revealed that the liver nodule was a PNET; hence, we completed the subtotal stomach-preserving pancreaticoduodenectomy 5 weeks after the first laparotomy. The patient received no adjuvant chemotherapy after surgery. Twenty-one months later, we discovered 20 scattered liver metastases via computed tomography; these were considered unresectable. Therefore, we administered everolimus for 7 months, but the patient developed interstitial pneumonia and experienced metastatic progression. Subsequent sunitinib administration for 6 months was ineffective. Finally, we chose STZ (1000 mg/m2, weekly) as a third-line treatment, which produced a partial response for 10 months. The patient remains alive 38 months after the detection of recurrence. As the order in which anti-cancer drugs should be administered to treat PNET has not been determined, additional predictors of their therapeutic efficacy should be investigated.