[FOLFIRI plus RAM Therapy in Later Line of Unresectable Colorectal Cancer].

FOLFIRI plus ramucirumab(RAM)therapy has been reported to be effective and safe in the RAISE trial as second-line treatment for unresectable colorectal cancer. It is hypothesized that RAM may be effective in patients with PD treated with FOLFIRI plus bevacizumab(Bev)due to different mechanism of action from that of Bev, which is also an angiogenesis inhibitor. From January 2017 to December 2021, we conducted a retrospective study of 6 patients who had PD with 5-FU, oxaliplatin, irinotecan, or Bev as first or second-line treatment at our institution and who received FOLFIRI plus RAM in later line treatment. The 6 cases consisted of 3 patients in the third-line treatment, 1 patient in the fourth-line treatment, and 2 patients in the sixth-line treatment. The anti-tumor effect was PD in all cases in the third-line and fourth-line treatment, but the 2 patients of sixth-line treatment were controlled diseases.

[A Case Report-A Successful Case of Distal Pancreatectomy with En Bloc Celiac Axis Resection for Locally Advanced Pancreatic Cancer with an Aberrant Right Hepatic Artery].

In cases of pancreatic cancer with anatomical variations of the hepatic artery, it is important to evaluate the hemodynamics of each case for surgical indication. We report the case of a 68-year-old man with locally advanced pancreatic cancer and an aberrant right hepatic artery who underwent distal pancreatectomy with celiac axis resection(DP-CAR). He was admitted to our institute due to abdominal discomfort. A CT scan showed pancreatic cancer invading the common hepatic artery. He underwent chemoradiotherapy with a diagnosis of locally advanced pancreatic cancer. After the tumor downstaging, we performed DP-CAR, which included a gastroduodenal artery and a proper hepatic artery resection. Even though delayed gastric emptying was observed after the operation, he was discharged on postoperative day 36.

Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery for descending colon cancer: a propensity score-matched analysis.

BACKGROUND: The clinical impact of single-incision laparoscopic surgery (SILS) for descending colon cancer (DCC) is unclear. The aim of this study was to evaluate the clinical outcomes of SILS for DCC compared with multi-port laparoscopic surgery (MPLS). METHODS: We retrospectively analyzed 137 consecutive patients with stage I-III DCC who underwent SILS or MPLS at two high-volume multidisciplinary tertiary hospitals between April 2008 and December 2018, using propensity score-matched analysis. RESULTS: After propensity score-matching, we enrolled 88 patients (n = 44 in each group). SILS was successful in 97.7% of the matched cohort. Compared with the MPLS group, the SILS group showed significantly less blood loss and a greater number of harvested lymph nodes. Morbidity rates were similar between groups. Recurrence pattern did not differ between groups. No significant differences were found between groups in terms of 3-year disease-free and overall survivals. CONCLUSION: SILS appears safe and feasible and can provide satisfactory oncological outcomes for patients with DCC.

Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery for rectosigmoid or upper rectal cancer.

BACKGROUND: Single-incision laparoscopic surgery (SILS) for rectal cancer is technically challenging, and its clinical impact is unclear. The aim of this study was to evaluate clinical outcomes of SILS for rectal cancer compared with multi-port laparoscopic surgery (MPLS). PATIENTS AND METHODS: We retrospectively analyzed 357 consecutive patients with stage I-III rectal cancer located in the rectosigmoid or upper rectum who underwent SILS or MPLS between January 2012 and December 2016, using propensity score-matched analysis. RESULTS: After propensity score-matching, we enrolled 204 patients (n = 102 per group). Before matching, significant group-dependent differences were observed in tumor location (p < 0.001). After matching, preoperative clinical factors were similar between groups. SILS was successful in 73.5% of cases, an additional port was required in 23.5%, and 2.9% were converted to open surgery. Compared to the MPLS group, the SILS group showed shorter operative time (192 vs. 211 min, p = 0.015) and shorter postoperative hospital stay (9 vs. 11 days, p = 0.038). Other operative factors and morbidity rates did not differ significantly between groups. The number of harvested lymph nodes was smaller in the SILS group (24) than in the MPLS group (27, p = 0.008). Postoperative recurrence did not differ between groups, either before or after matching. No significant differences in 3-year disease-free, 3-year local recurrence-free, or 5-year overall survival were found between groups. CONCLUSIONS: SILS is safe, is feasible, and offers satisfactory oncological outcomes in selected patients with rectosigmoid or upper rectal cancer.

TRESBIEN (OGSG 2101): encorafenib, binimetinib and cetuximab for early recurrent stage II/III BRAF V600E-mutated colorectal cancer.

The BRAF V600E mutation accounts for approximately 5% of colorectal cancer (CRC) cases and is an extremely poor prognostic factor. However, there are no clear recommendations regarding first-line therapy for patients with early recurrent BRAF V600E-mutated CRC, during or after adjuvant chemotherapy. Recently, a novel combination of encorafenib, binimetinib and cetuximab, showed a higher response rate than standard chemotherapy in patients with BRAF V600E-mutated CRC. Here we describe our plan for the TRESBIEN study (OGSG 2101), which is an open-label, multicenter, single-arm, phase II study designed to evaluate whether encorafenib, binimetinib and cetuximab are effective for patients with early recurrent BRAF V600E-mutated colorectal cancer, during or after adjuvant chemotherapy. The planned number of subjects is 25.

An ongoing study to evaluate encorafenib, binimetinib and cetuximab for people with early recurrent BRAF V600E-mutated colorectal cancer. BRAF V600E-mutated colorectal cancer (CRC) is a type of cancer caused by change (mutation) in a gene called BRAF. It is one of the most difficult types of CRC to treat because currently available drugs do not effectively treat the disease. Recently, two novel treatments, encorafenib and cetuximab, have been approved for use together in several countries for the treatment of advanced or metastatic BRAF V600E-mutated CRC. In Japan, these drugs are also approved to be given with another treatment called binimetinib, an approach called triplet therapy. This article describes the ongoing TRESBIEN study that is looking at how effective and how safe triplet therapy is for the treatment of people with early recurrent BRAF V600E-mutated CRC, during or after they have additional (adjuvant) chemotherapy. This study is ongoing, and the researchers are currently recruiting new participants. TRESBIEN will evaluate the percentage of participants whose tumors shrink with triplet therapy. The study will also look at any side effects. Clinical Trial Registration: jRCTs051210152 (ClinicalTrials.gov) (Japan Registry of Clinical Trials https://jrct.niph.go.jp/search?language=en&page=1).

Long-term outcomes of single-incision versus multiport laparoscopic colectomy for colon cancer: results of a propensity score-based analysis.

BACKGROUND: Long-term outcomes of single-incision laparoscopic colectomy (SILC) for colon cancer (CC), as practiced in real-world settings, especially in relation to disease stage, have not been established. We examined, retrospectively, both short- and long-term outcomes of SILC versus those of multiport laparoscopic colectomy (MPLC) performed for CC in a propensity-score-matched cohort. METHODS: The study involved 263 patient pairs matched 1:1 from among 691 patients who, between January 2008 and May 2014, underwent either SILC or MPLC for a primary solitary CC at our hospital. Short-term and long-term operative outcomes were compared between the two groups. RESULTS: Operation time was the only surgical outcome that varied significantly between the two groups (p = 0.0004). Overall 5-year cancer-specific survival (CSS) in the SILC group was 93.7 (95% CI 89.6-96.2)%, and CSS per pathological stage (I, II and III) was 98.5 (90.0-99.8)%, 96.0 (88.2-98.7)%, and 88.3 (79.6-93.6)%, respectively, whereas overall 5-year CSS in the MPLC group was 93.3 (89.4-95.9)%, and CSS per pathological stage was 100%, 95.4 (88.3-98.3)%, and 84.1 (74.1-90.8)% (p = 0.5278, 0.2679, 0.7666, and 0.9073), respectively. Overall 3-year disease-free survival (DFS) in the SILC group was 94.0 (90.2-96.4)%, and 3-year DFS per pathological stage was 98.6 (90.4-99.8)%, 90.1 (81.4-95.0)%, and 79.0 (69.4-86.2)%, respectively, whereas overall 3-year DFS in the MPLC group was 93.2 (89.4-95.7)%, and 3-year DFS per pathological disease stage was 100%, 94.5 (87.4-97.7)% and 75.5 (64.7-83.8)% (p = 0.2829, 0.7401, 0.4335 and 0.8518), respectively. Thus, oncological outcomes did not differ significantly between groups. Incisional hernia occurred in 21 (8.0%) SILC group patients and 17 (6.5%) MPLC group patients, without a significant between-group difference (p = 0.6139). CONCLUSION: Our data indicate that perioperative and oncological outcomes of SILC performed for CC are comparable to those of MPLC performed for CC.

Short- and Long-Term Outcomes of Single-Incision Laparoscopic Surgery for Right-Side Colon Cancer.

INTRODUCTION: There are little data concerning the long-term outcome of single-incision laparoscopic surgery (SILS) for colon cancer. Therefore, we investigated not only the short-term outcomes but also the long-term outcomes of SILS for right-side colon cancer. METHODS: We retrospectively compared short- and long-term outcomes of SILS and conventional laparoscopic surgery (CLS) for right-sided colon cancer in our institution. Intergroup differences of short-term outcomes were evaluated using χ2 or Fisher exact tests and 2-sample Student t tests. The disease-free survival rates (long-term outcome) of stage II and III patients were estimated using the Kaplan-Meier method and compared using log-rank tests. RESULTS: There were 290 operations conducted for right-side (cecum and ascending) colorectal cancers from April 2011 to July 2018. Open surgery was performed in 12 cases from start to the operation. SILS was performed in 196 cases and CLS in 55 cases. One patient underwent intraoperative conversion from SILS to laparotomy for bleeding control. In addition, 1 port was added to SILS in 3 cases. These 4 cases were included in the analysis as the SILS group according to the principle of intent to treat. BACKGROUND: Factors including age, gender, body mass index, performance status, and tumor stage were not statistically different between the SILS and CLS groups. In short-term outcomes, the number of harvested lymph nodes was not statistically different. SILS required less operating time (p < 0.001) and resulted in a reduced bleeding volume (p < 0.001). There was no statistical difference in the frequency of overall complications (p = 0.06). The disease-free survival of stage II and III patients was not statistically different between the 2 groups. CONCLUSIONS: With the proper adaptation of SILS by an experienced surgeon, the short- and long-term outcomes of SILS were not inferior to those of CLS. Therefore, SILS could be a treatment option for right-sided colon cancer.

Index for the appropriate vancomycin dosing in premature neonates and infants.

BACKGROUND: In neonates, vancomycin (VCM) is used to treat Gram-positive bacterial infections. However, VCM blood concentrations are affected by gestational age, bodyweight (BW), and renal function. The initial VCM dose adjustment can therefore be difficult, and few reports have evaluated this issue. In this study, we investigated the factors determining the appropriate VCM dosing schedule in neonates, especially premature infants. METHODS: The VCM dosage and trough concentrations were retrospectively investigated from the initial treatment to maintenance therapy in neonatal intensive care unit patients who underwent therapeutic drug monitoring. We examined the average single-administration VCM dosage during maintenance therapy. We then compared the actual VCM dose with that calculated using an index comprising six items that influence the VCM daily dose (postnatal age, gestational age, BW, serum creatinine level, urine output, and lactate level). RESULTS: Twenty premature infants were included. The average BW of patients at the initial VCM administration was 975 g. During maintenance therapy, the average VCM dose was 8.4 mg/kg, and the median trough concentration was 12.4 µg/mL. When we applied the six-item index, 18 of 20 patients (90%) had concordant results between the actual VCM dosing schedule and the VCM calculated using the index. CONCLUSIONS: The average VCM dose and six-item index can facilitate the transition from the initial VCM dose to an appropriate dose in many cases and contribute to early treatment in low-birthweight infants with more variable BW, distribution volumes, and renal function. In conclusion, our six-item index may help standardize VCM administration in premature infants.

[Effect of Endoscopic Resection on Prognosis in T1b Colorectal Cancer].

With the advancement of endoscopic resection(ER)of colorectal cancer, surgical resection after ER has been increasing. This study evaluated the effects of initial ER on short- and long-term outcomes in T1b colorectal cancer. This retrospective cohort study enrolled patients with pathological T1b colorectal cancer who underwent colorectal surgical resection between 2008 and 2018. A total of 239 eligible patients were divided into 2 groups: patients initially treated using surgical resection with lymph node dissection(LND)(surgery alone, n=142)and patients treated using initial ER and additional surgical resection with LND(surgery after ER, n=97). No significant differences were observed in short-term outcomes(ie, operative time, blood loss, or postoperative complications)or the long-term outcomes(ie, recurrence rate, overall survival rate, or recurrence free survival rate)between groups.

[A Case of Carcinomatous Meningitis from Gastric Cancer with Improvement of QOL by Ventriculoperitoneal Shunt].

In cases where carcinomatous meningitis leads to hydrocephalus and increases intracranial pressure, patients present with exacerbated pain and several neurological symptoms. It is reported that multidisciplinary therapy, including radiation therapy, drug therapy, and surgery, is performed for patients with carcinomatous meningitis; however, it is rarely successful. Ventriculoperitoneal shunting(V-P shunt)is a surgical intervention that might relieve the pain temporarily and improve the quality of life. VPS should be taken into consideration in line with patients' and their families' intentions since the overall survival is fairly short.

[A Long-Survival Case of Lower Rectal Cancer with Unresectable Liver Metastases Treated with FOLFOXIRI plus Bevacizumab(BEV)].

A woman in her 30s visited our hospital complaining primarily of melena. Colonoscopy revealed the presence of a type 1 tumor in 2 cm from anal verge. Contrast-enhanced CT showed an unresectable massive liver metastasis in the left lobe of the liver and another metastasis in the right lobe. The patient received front-line chemotherapy with Leucovorin, fluorouracil, oxaliplatin, and irinotecan(FOLFOXIRI)plus bevacizumab(BEV). A year later, a marked reduction of liver metastases and primary lesions was confirmed by CT scan imaging. A multidisciplinary team recommended resection of the liver metastases followed by laparoscopic intersphincteric resection for primary lesions. However, after 1 year, a recurrence was diagnosed in the liver; hence, FOLFOXIRI plus BEV was reintroduced for volume reduction. The patient underwent a repeat hepatectomy since enough volume reduction was confirmed. One year later, she experienced a re-relapse of the metastasis in the liver. Currently, she is still undergoing chemotherapy following 7 years since the first visit. Long-term survival can be expected following surgical treatment during chemotherapy.

[Nodular Lymphocyte-Predominant Hodgkin Lymphoma(NLPHL)Which Originate from the Mesentery-A Series of Two Cases].

Nodular lymphocyte-predominant Hodgkin lymphoma(NLPHL)is a subtype of Hodgkin lymphoma. It is uncommon in Japan, and only a few cases of NLPHL originating from the mesentery have been reported. Most patients with NLPHL present in the early stage, but some patients have malignancy at initial presentation. We should perform staging laparotomy for the diagnosis and treatment of cases in which a lymph node biopsy is difficult.

[Case Series of the TAS-102 plus Bevacizumab(Bev)Combination Therapy in Unresectable Advanced Colorectal Cancer].

A phase-Ⅱtrial of TAS-102 plus bevacizumab(Bev)combination therapy showed a progression-free survival(PFS)of 3.7-4.6 months. Here, we report 12 cases of unresectable advanced recurrent colorectal cancer treated with TAS-102 plus Bev therapy at our hospital between June 2017 and February 2020. The median PFS was 6 months(2-12). Adverse events greater than Grade 3 were neutropenia(33.3%), febrile neutropenia(8.3%), thrombocytopenia(8.3%), and vomiting (8.3%). The frequency of non-hematotoxicity was low. In conclusion, the TAS-102 plus Bev therapy may be a useful option for the late-line treatment of unresectable advanced recurrent colorectal cancer.

[Launching Robot-Assisted Laparoscopic Surgery for Rectal Cancer in Our Hospital-Short-Term Results].

Robot-assisted laparoscopic surgery(RALS)for rectal cancer has been covered by National Health Insurance in Japan since April 2018. We launched RALS in our hospital in October 2019 and now report the short-term results(up to January 2020). Altogether, 15 consecutive patients(12 men, 3 women: median age 70 years)with rectal cancer underwent RALS during that period. For the first 2 cases, we performed RALS under the instruction of an experienced proctor from another institution. Among the 15 patients, 6 underwent high anterior resection and 9 low anterior resection. Median operating time was 358 min, median intraoperative blood loss was 0 mL, and there were no apparent intraoperative complications. Median postoperative length of hospital stay was 13 days, and only 1 patient developed a high-grade complication(Clavien-Dindo Grade Ⅲb)postoperatively. Hence, RALS for rectal cancer was launched successfully in our institution.

[A Case of Slow-Growing Intrahepatic Cholangiocarcinoma after Resection of Gastric Cancer].

An 83-year-old woman was given a diagnosis of gastric cancer and received distal gastrectomy 9 years ago. Three years later, CT revealed a tumor measuring 13 mm in diameter in hepatic segment 7. She was followed for 5 years, and the size of the tumor did not change. Eight years later after gastrectomy, the tumor size slightly enlarged to 17 mm, and biopsy revealed adenocarcinoma. The patient underwent liver resection of segment 7. The pathological diagnosis was well differentiated intrahepatic cholangiocarcinoma(ICC). No sign of recurrence has been found during a 1-year. This case, in which the patient was followed for 5 years before curative surgical treatment, is significant, because it demonstrates the slow-growing nature of ICC.

[A Case of Robot-Assisted Abdominoperineal Resection for Local Control for Lower Rectal Cancer with Synchronous Liver and Lung Metastases].

The patient was a 70s woman who was referred to our hospital with a complaint of bloody stool. Colonoscopy revealed type 2 tumor at a distance of 1 cm from the dentate line, without obstruction. The pathological diagnosis was adenocarcinoma. Enhanced CT revealed a tumor at the rectum below peritoneal reflection as well as swelling of the mesorectal lymph nodes. Multiple liver and lung metastases were also observed. The diagnosis was lower rectal cancer cT4aN2M1b(H2, PUL2), cStage Ⅳ. Chemotherapy was performed for disease control because of unresectable metastases. She received 7 courses of mFOLFOX plus bevacizumab. Further, as the metastatic lesion was inhibited, the primary lesion was excised for the purpose of symptom control. We judged that sphincter preservation was impossible because it was 1 cm away from the dentate line. She underwent robot-assisted abdominoperineal resection with D3 lymphadenectomy and sigmoid colostomy.

[A Case of Solitary Fibrous Tumor of the Liver].

Most solitary fibrous tumors(SFT)occur in the thoracic cavity and reports on liver SFT are very rare. We encountered a case of SFT of the liver, and thus, decided to report it with a review of literature. A 70-year-old man was informed of a liver tumor by his previous doctor and referred to us for further examination and treatment. Contrast-enhanced CT revealed a 3.5 cm cyst in the S2/3 of the liver and a 3.2 cm tumor with an early staining within the cyst. Laparoscopic lateral segmentectomy was performed and a diagnosis of hepatic cystic adenocarcinoma was made. Macroscopically, the tumor was white and welldefined. Histopathological examination revealed round chromatin-enriched tumor cells proliferated with round fibrillar cells or intercalated structures consisting of round or short spindle-shaped cells. Immunohistochemistry yielded negative results for CAM5.2, HepPar1, CD31, CD99, SMA, and HMB45 but positive results for CD34, Factor Ⅷ, Bcl-2, and STAT6; therefore, the patient was further diagnosed with liver SFT. Although liver SFT is rare, it was considered a differential diagnosis when multiple bloody liver tumors were detected. In addition, since there were reports of recurrence, careful follow-up in future, was deemed necessary.

[A Case of Complete Pathological Response in a Patient with Advanced Ascending Colon Cancer That Invaded the Liver and Duodenum after FOLFOXIRI plus Bevacizumab Chemotherapy].

A 71-year-old woman with advanced ascending colon cancer was admitted to our hospital. Abdominal computed tomography( CT)revealed locally advanced sigmoid colon cancer with suspected invasion of the liver and duodenum. The clinical stage of the disease was cT4bN3M1a, cStage Ⅳa, with wild-type RAS and UGT1A1 expression. An ileostomy was performed because of bowel obstruction. The patient received 6 courses of FOLFOXIRI plus bevacizumab(Bev). The only adverse event was Grade 3 neutropenia. Laparoscopic right hemicolectomy with lymph node dissection was performed. The pathological diagnosis was the absence of viable, Grade 3 carcinoma cells. This result suggested that preoperative FOLFOXIRI plus Bev chemotherapy is useful for the treatment of locally advanced colon cancer.

[A Resected Case of Hepatocellular Carcinoma Recurrence with Bile Duct Tumor Thrombus after RFA].

Hepatocellular carcinoma with bile duct invasion is rare, with a reported incidence of 3.4%. A 71-year-old man with hepatocellular carcinoma underwent radiofrequency ablation(RFA)(S6, S7, S8)and required readmission 22 months after the RFA for hepatocellular carcinoma recurrence detected by gadoxetic acid-enhanced magnetic resonance imaging. Enhanced abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a tumor thrombus in a biliary branch and left adrenal gland metastases. We performed a right lobectomy and left adrenalectomy. The biliary thrombus was easily removed. Postoperative histopathological examination of the resected specimen showed a moderately differentiated hepatocellular carcinoma invading the biliary tract and the absence of viable cells in the liver tumor. The patient has shown no recurrence 6 months after the hepatectomy.

[Long-Term Survival in a Patient with Stage â £ Gastric Cancer Successfully Treated with Multidisplinary Treatment].

A man in his 60s who had epigastric pain was referred to our hospital and diagnosed with advanced type 3 gastric cancer with multiple liver metastases, cT4acN2cN1(H1), cStage Ⅳ(HER2 3+). He underwent chemotherapy using capecitabine, cisplatin(CDDP), and trastuzumab(T-mab)(XPT). After 7 courses of XPT and 23 courses of XT, liver metastases disappeared, and we decided to perform open distal gastrectomy, D2+ #18 lymphadenectomy, and Billroth Ⅰ reconstruction as a conversion surgery. Despite adjuvant chemotherapy with S-1 plus T-mab, multiple lymph nodes recurrence occurred 3 months after the surgery. He was found to be in complete remission as assessed by CT after 5 courses of second-line CPT-11 treatment, which was discontinued after 17 courses. The patient is alive without recurrence at 57 months after the initial treatment and 22 months after the last treatment.