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.

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.

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.

Clinical significance of evaluating endoscopic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Clinical significance of endoscopic response (ER) after neoadjuvant chemotherapy (NAC) for esophageal cancer has not been fully understood. Thus, the present study aimed to investigate the association between ER to NAC and its clinicopathological outcomes in patients with esophageal squamous cell carcinoma (ESCC). METHODS: In total, 141 patients who underwent NAC and subsequent esophagectomy for ESCC were included. ER to NAC was retrospectively evaluated based on macroscopic findings of the primary tumor, which was classified into three categories: endoscopic no response (eNR), endoscopic partial response (ePR), and endoscopic good response (eGR). An endoscopic responder was defined as patients with eGR/ePR. RESULTS: Approximately 89.4% of patients had cStage II-III disease, and 7.1% had pathological complete response. Upon ER evaluation, eNR, ePR, and eGR were observed in 46 (32.6%), 54 (38.3%), and 41 (29.1%) patients, respectively. Pathological responders significantly increased as the ER grade became better. Among preoperative clinical factors, only ER significantly correlated with pathological response in univariate and multivariate analysis. Endoscopic responders showed a significantly better prognosis than did eNR patients (P < 0.001), although the overall survival (OS) of the patients with eGR and ePR was equivalent. Endoscopic responder, ypT, ypN, and pathological responder were significant predictors of OS in the univariate analysis, and endoscopic responder, ypN, and pathological responder were independent predictors in the multivariate analysis. CONCLUSION: This study suggests that ER can be a simple and important tool to predict the pathological response and survival of patients who undergo NAC for ESCC.

[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.

Preoperative controlling nutritional status (CONUT) is useful to estimate the prognosis after esophagectomy for esophageal cancer.

PURPOSE: The aim of this study is to confirm the predictive value of controlling nutritional status (CONUT), as a postoperative prognostic marker for esophageal cancer patients undergoing esophagectomy. METHODS: We retrospectively analyzed 373 patients who underwent three-incision esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and March 2016. The patients were divided into three groups based on the degree of preoperative malnutrition as assessed by CONUT: normal, light malnutrition, and moderate or severe malnutrition. RESULTS: The patients with moderate or severe malnutrition experienced a significantly higher frequency of reoperation (normal or light malnutrition, 6.3%; moderate or severe malnutrition, 18.2%; P = 0.033) and a higher tendency for respiratory morbidities (normal or light malnutrition, 14.0%; moderate or severe malnutrition, 27.3%; P = 0.088). Cox regression analysis identified a significantly poor prognosis, in both overall survival (hazard ratio (HR), 3.56; 95% confidence interval (CI), 1.714-7.390; P < 0.001) and cancer-specific survival (HR, 3.41; 95% CI, 1.790-6.516; P = 0.046). CONCLUSIONS: CONUT is convenient and useful for preoperatively assessing malnutrition and prognosis of esophageal cancer patients who underwent surgery.

Late Recurrence After Radical Resection of Esophageal Cancer.

BACKGROUND: Approximately 10-20 % of esophageal cancer patients in whom recurrence is diagnosed experience late recurrence beyond 2 years after esophagectomy. However, the risk of late recurrence is still unclear. The aim of this study was to identify the risk factors of late recurrence for appropriate postoperative surveillance. METHODS: A total of 447 patients underwent radical esophagectomy and reconstruction for esophageal cancer from 2005 to 2014. Patients who had recurrence beyond 2 years after esophagectomy were defined as the late recurrence group and the remaining patients with recurrence as the early recurrence group. A comparison of the clinicopathological factors and prognosis was performed between patients with early recurrence, late recurrence, and no recurrence. RESULTS: Recurrences were recognized in 117(26.2 %) of the 447 patients. Recurrence was diagnosed within 2 years after surgery in 103 patients (88.0 %) and after 2 years in 14 patients (12.0 %). Patients with late recurrence showed a favorable prognosis compared with those with early recurrence (P = 0.0131), and late recurrence was an independent factor associated with a favorable prognosis after recurrence (HR 0.199, P = 0.025). In the comparison between patients with late recurrence and those with no recurrence who had a minimal recurrence-free survival of 2 years, pathological lymph node metastasis at esophagectomy was found to be an independent predictor of late recurrence (HR 7.296, P = 0.043). CONCLUSIONS: Pathological lymph node metastasis at esophagectomy is a risk factor of late recurrence for esophageal cancer, and a close, lifelong follow-up is recommended for such patients.

Sarcopenia is a Predictor of Postoperative Respiratory Complications in Patients with Esophageal Cancer.

BACKGROUND: Depletion of skeletal muscle mass (sarcopenia) indicates a poor prognosis for patients with several kinds of cancer, but it remains unclear whether esophageal squamous cell carcinoma (ESCC) is among these cancers. The aim of this study was to clarify the relationship between sarcopenia and postoperative outcome in patients with ESCC treated by esophagectomy. METHODS: Skeletal muscle mass was assessed in 138 patients who underwent esophagectomy from August 2009 to May 2014. A multifrequency bioelectrical impedance analysis (InBody 720; Biospace, Tokyo, Japan) was used to assess skeletal muscle mass just before surgery. Postoperative complications were graded according to the Clavien-Dindo classification, and univariate and multivariate analyses were performed for postoperative respiratory complications. RESULTS: Sarcopenia was determined in 61 patients (44.2 %). Preoperative pulmonary function was significantly lower and the rate of respiratory complications significantly higher in the sarcopenia group than in the non-sarcopenia group (p < 0.01). For other complications, the differences were not significant. Multivariate analysis showed that sarcopenia [odds ratio (OR) 5.82; p = 0.0001] and longer operation time (OR 3.09; p = 0.04) were risk factors for the occurrence of respiratory complications. CONCLUSIONS: Sarcopenia may be a predictor of pulmonary complications after esophagectomy. Further analysis is needed to clarify whether nutritional intervention improves skeletal muscle mass and thus contributes to reducing postoperative respiratory complications in sarcopenic patients.

Diagnostic laparoscopic biopsy for intraabdominal tumors.

Improvements in imaging technology have resulted in an increase in the incidental detection of intraabdominal tumors. Diagnostic computed tomography (CT)- and ultrasound (US)-guided biopsy, while minimally invasive, often provides specimens that are insufficient for histological evaluation. Moreover, it can be difficult to perform because the location and size of the tumor. In such cases, laparoscopic biopsy is useful because it is less invasive than laparotomy, but more reliable than imaging-guided biopsy, to obtain a sufficient specimen, regardless of the location and size of the tumor. We report a series of seven patients who underwent laparoscopic biopsy of intraabdominal tumors of unknown origin. There were no cases of conversion to laparotomy and all patients were able to resume oral intake on postoperative day 1. There were no intraoperative or postoperative complications. Thus, laparoscopic biopsy for a tumor of unknown origin is useful and minimally invasive.

Original scoring system for predicting postoperative morbidity after esophagectomy for esophageal cancer.

PURPOSE: Postoperative morbidity remains common after esophagectomy. There are currently few tools that can be used to estimate the incidence of complications. This study aimed to create a novel scoring system for predicting postoperative morbidity. METHODS: A total of 365 patients who underwent elective esophagectomy with two- or three-field lymphadenectomy for esophageal cancer were retrospectively analyzed. Patients were divided into development (n = 250) and validation datasets (n = 115). A scoring system was established by specifying the expected morbidity incidence values for all independent predictors in the development dataset, after which, the reproducibility was confirmed in the validation dataset. RESULTS: The incidence of any morbidity was 44.7 %. Male sex, severe emaciation (body mass index <18), a lower performance status (grade 1 or 2), operation ≥540 min and massive bleeding (blood loss/body weight ≥20) were independent predictors of postoperative morbidity. The total of all predictive scores was calculated. The incidence of any morbidity and of severe morbidity (Clavien-Dindo classification ≥IIIb) significantly correlated with the score after dividing the scores into three groups (≤8, 10 and 11 and ≥13). This finding was also confirmed in the validation dataset. CONCLUSION: The current scoring system is considered to be useful for predicting postoperative morbidity after esophagectomy.

Advantages of FDG-PET/CT over CT alone in the preoperative assessment of lymph node metastasis in patients with esophageal cancer.

PURPOSE: The aim of this study was to determine the benefits of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) compared to CT alone in the preoperative assessment of lymph node metastasis in patients with esophageal cancer. METHODS: One-hundred and seven patients who underwent esophagectomy with lymph node dissection between March 2007 and December 2009 were eligible. Sixty-seven patients were treated with surgery alone (SA group), while 40 patients received preoperative treatment prior to surgery (PT group). The pathological results of 1,403 dissected lymph node stations were compared with the results obtained using each imaging modality. RESULTS: PET/CT showed a significantly higher specificity and positive predictive value (PPV) than CT alone (97.7 vs. 94.1 % and 64.6 vs. 44.0 %, respectively), when analyzed by the lymph node stations. The PPV of PET/CT for N1 cases was significantly better than that of CT alone (78.9 vs. 53.9 %), particularly in the PT group (91.3 vs. 65.4 %). Among the patients in the SA group, the number of metastatic nodes was significantly higher in PET-N1 cases than in PET-N0 cases (5.78 vs. 1.90). CONCLUSION: PET/CT is useful for selecting patients with multiple lymph node metastases and also for detecting residual metastatic nodes after PT, and thus is beneficial to decide on the appropriate treatment strategy for patients with esophageal cancer.

A clinicopathological analysis of primary mucosal malignant melanoma.

PURPOSES: Primary mucosal malignant melanoma (PMMM) is a rare and highly lethal neoplasm associated with a poor prognosis. CXC chemokine receptor 4 (CXCR4) is expressed on various tumor cells, including malignant melanoma. Recent data indicate that CXCL12 and CXCR4 play a critical role in the behavior of cancer cells and in the survival of cancer patients. However, there has been no study that has addressed the expression and function of CXCR4/CXCL12 signaling in PMMM. METHODS: Immunohistochemical staining for CXCL12 and Ki67 in biopsy tissues from 10 cases of PMMM was performed. We analyzed the correlations between the clinicopathological features and expression levels of CXCL12 and Ki67. RESULTS: Six cases showed a high level of CXCL12 expression, while four cases had a low level of expression. High expression of CXCL12 correlated with a poor prognosis, although statistical significance was not reached (p = 0.054). Ki67 was highly expressed in five cases, while the expression in the other five cases was low. There was no correlation between the Ki67 expression and prognosis. CONCLUSIONS: The findings of this study suggest that CXCL12 expression may play an important role in the biological behavior of PMMM and may be associated with a poor prognosis of PMMM patients.

Changes in body composition secondary to neoadjuvant chemotherapy for advanced esophageal cancer are related to the occurrence of postoperative complications after esophagectomy.

BACKGROUND: Although a survival benefit of neoadjuvant treatment for patients with esophageal cancer has been highlighted, the influence of neoadjuvant treatment on the nutritional status of patients with esophageal cancer is not well understood. METHODS: Changes in body composition parameters were assessed in 30 patients who underwent neoadjuvant chemotherapy (NAC) comprising docetaxel, cisplatin, and 5-fluorouracil followed by esophagectomy from August 2009 to April 2013. Body composition was evaluated before and after NAC using multifrequency bioelectrical impedance analysis (InBody 720; Biospace, Tokyo, Japan). Postoperative complications were graded according to the Clavien-Dindo classification. RESULTS: Twenty-three postoperative events occurred in 16 patients. A decrease in body protein was observed in 13 patients (43.3 %), while skeletal muscle (SM), body cell mass (BCM), and fat-free mass (FFM) declined in 11 patients (36.7 %) during NAC. Changes in these four parameters during chemotherapy significantly differed between patients with postoperative complications and those without: protein, -1.6 ± 0.9 versus +4.4 ± 2.1 kg (P = 0.01); SM, -1.3 ± 1.1 versus +4.7 ± 2.4 kg (P = 0.02); BCM, -2.4 ± 1.6 versus +3.8 ± 2.2 kg (P = 0.03); and FFM, -1.4 ± 1.4 versus +4.3 ± 2.3 kg (P = 0.04). CONCLUSIONS: Changes in body composition parameters are possible predictive markers of postoperative complications after esophagectomy after NAC. Further analysis is needed to clarify whether nutritional intervention improves such parameters and thus contributes to reduced postoperative morbidity.

The Success Rate Is Lower but Completion Rate of Laparoscopic Cholecystectomy Is higher in Endoscopic Transpapillary Gallbladder Drainage than Percutaneous Gallbladder Drainage for Acute Cholecystitis.

BACKGROUND: We investigated the success and complication rates of endoscopic transpapillary gallbladder drainage (ETGBD) and percutaneous transhepatic gallbladder drainage (PTGBD) and the outcomes of subsequent cholecystectomy for acute cholecystitis. METHODS: Patients (N=178) who underwent cholecystectomy after ETGBD or PTGBD were retrospectively assessed. RESULTS: ETGBD was successful in 47 (85.5%) of 55 procedures, whereas PTGBD was successful in 123 (100%) of 123 sessions (P<0.001). Complications related to ETGBD and PTGBD occurred in 6 (12.8%) of 47 and 16 (13.0%) of 123 patients, respectively (P=0.97). After propensity matching, 43 patients from each group were selected. Median time from drainage to cholecystectomy was 48 (14 to 560) days with ETGBD and 35 (1 to 90) days with PTGBD (P=0.004). Laparoscopy was selected more often in the ETGBD group (97.7%) than in the PTGBD group (79.1%) (P=0.007), and conversion from laparoscopy to open cholecystectomy was more common with PTGBD (41.2%) than with ETGBD (7.1%) (P<0.001). Mean operation time was significantly shorter with ETGBD (135.8±66.7 min) than with PTGBD (195.8±62.2 min) (P<0.001). The incidence of Clavien-Dindo grade ≥III postoperative complications was 9.3% with ETGBD and 11.6% with PTGBD (P=0.99). CONCLUSIONS: The success rate is lower but completion of laparoscopic cholecystectomy is more in endoscopic gallbladder drainage than percutaneous gallbladder drainage for acute cholecystitis.

A rare incidence of a hepatic artery pseudoaneurysm following plastic biliary stent insertion.

Hepatic artery pseudoaneurysms have been reported to occur in approximately 1% of cases after metal stenting for malignant biliary obstruction. In contrast, only a few cases have been reported as complications after plastic stenting for benign biliary disease. We report a 61-year-old man with cholangitis who presented with a rare complication of hemobilia after implantation of 7 Fr double pigtail plastic biliary stents. No bleeding was observed approximately one month after biliary stent tube removal. Contrast-enhanced CT scan revealed a circularly enhanced lesion (5 mm in diameter) in the arterial phase at the tip of the previously inserted plastic bile duct stent. Color Doppler ultrasonography enhanced the lesion and detected arterial blood flow inside. He was diagnosed with a hepatic artery pseudoaneurysm. However, he had no risk factors such as prolonged catheterization, severe cholangitis, liver abscess, or long-term steroid use. Superselective transarterial embolization using two metal microcoils was successfully completed without damage to the surrounding liver parenchyma. If hemobilia is suspected after insertion of a plastic bile duct stent, immediate monitoring using contrast-enhanced computed tomography or Doppler ultrasonography is recommended.

Hepatic hemangioma in a simple liver cyst mimicking biliary cystic neoplasm.

BACKGROUND: Follow-up is recommended for an asymptomatic unilocular hepatic cystic lesion without wall-thickness and nodular components. A few liver cystic lesions represent biliary cystic neoplasms, which are difficult to differentiate from simple cysts with benign mural nodules on imaging alone. CASE PRESENTATION: An 84-year-old woman with a history of simple liver cyst diagnosed one year prior was admitted for evaluation of a developed mural nodule in the cystic lesion. She had no specific symptoms and no abnormalities in blood tests except for carcinoembryonic antigen (5.0 ng/mL) and carbohydrate antigen (43.5 U/mL) levels. Contrast-enhanced computed tomography revealed a well-defined, low-attenuation lesion without a septum that had enlarged from 41 to 47 mm. No dilation of the bile duct was observed. A gradually enhancing mural nodule, 14 mm in diameter, was confirmed. MRI revealed a uniform water-intense cystic lesion with a mural nodule. This was followed by T2-enhanced imaging showing peripheral hypointensity and central hyperintensity. Enhanced ultrasonography revealed an enhanced nodule with a distinct artery within it. A needle biopsy of the wall nodule or aspiration of intracystic fluid was not performed to avoid tumor cell spillage. The possibility of a neoplastic cystic tumor could not be ruled out, so a partial hepatectomy was performed with adequate margins. Pathologically, the cystic lesion contained a black 5 mm nodule consisting of a thin, whitish fibrous wall and dilated vessels lined by CD31 and CD34 positive endothelial cells. The final diagnosis was a rare cavernous hemangioma within a simple liver cyst. CONCLUSIONS: Cavernous hemangiomas mimicking well-enhanced mural nodules can arise from simple liver cysts. In less malignant cases, laparoscopic biopsy or percutaneous targeted biopsy of the mural nodules, together with needle ablation, may be recommended to avoid unnecessary surgery.

Preventive effect of sivelestat on postoperative respiratory disorders after thoracic esophagectomy.

PURPOSE: Sivelestat, a selective inhibitor of neutrophil elastase, has been reported to reduce acute lung injury associated with systemic inflammatory response syndrome. This study retrospectively investigated the effect of sivelestat on respiratory function in patients who underwent esophagectomy. METHODS: Patients who underwent esophagectomy for thoracic esophageal cancer between 2005 and 2010 were included in this study. Forty-two were treated perioperatively with sivelestat (4.8 mg/kg/day; sivelestat group) and the remaining 35 were not (control group). Sivelestat was administered continuously from the beginning of surgery until postoperative day 3. All patients were administered methylprednisolone for 3 days. The perioperative clinical and laboratory data, total sequential organ failure assessment score, PaO2/FiO2 ratio (P/F ratio) and postoperative complications were compared between the two groups. RESULTS: There were no significant differences between the groups in the patients' background data. The P/F ratio immediately after surgery was significantly higher in the sivelestat group than in the control group (p < 0.05). The respiratory rate immediately after surgery and the temperature on postoperative day 2 were significantly lower in the sivelestat group than in the control group (p < 0.05). There were no differences in any of the other clinical data or complications. CONCLUSIONS: Perioperative administration of sivelestat improves postoperative respiratory function in patients after esophagectomy.

Surgery for Hepatocellular Carcinoma With Macroscopic Vascular Invasion in the Era of Modern Molecular Therapy.

It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors has shown promising results in patients with metastatic hepatocellular carcinoma; however, molecular therapy is limited to patients with Child-Pugh class A disease. This review summarizes the present status of surgical therapies, including conversion hepatectomy, for patients with MVI in the developing era of novel molecular therapy. Phase III studies showed patients with macroscopic vascular invasion had significant survival benefits from sorafenib [hazard ratio (HR)=0.68] and regorafenib (HR=0.67) versus placebo, and nivolumab (HR=0.74) versus sorafenib. Lenvatinib and atezolizumab plus bevacizumab showed marginal effects. It is currently widely assumed that molecular therapy alone will not cure the disease but that additional conversion hepatectomy will be required. A response other than progressive disease is essential but a pathological complete response is not always required. A significant randomized controlled trial has already started in China to assess the necessity for conversion hepatectomy after effective atezolizumab plus bevacizumab treatment, and the results are still awaited. According to Japanese national data, upfront hepatectomy can be recommended for patients with initially resectable disease and macroscopic vascular invasion other than for those with tumors in the main portal vein and the inferior vena cava. In addition, adequate adjuvant therapies with hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial but an effective adjuvant molecular therapy is currently unavailable. In conclusion, novel molecular therapies with higher response rates customized to the oncologic characteristics of each hepatocellular carcinoma with macroscopic vascular invasion are needed to increase the likelihood of conversion surgery and improve long-term outcomes.

Durable Stable Disease by Atezolizumab/Bevacizumab Can Provide Long-term Survival of Patients With Hepatocellular Carcinoma Lung Metastases.

BACKGROUND: Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response. CASE REPORT: A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child-Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child-Pugh Grade of A and a performance status of 0. CONCLUSION: Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life.