Plasma-derived candidate biomarkers for detection of gallbladder carcinoma.

Gallbladder carcinoma (GBC) is a major cancer of the gastrointestinal tract with poor prognosis. Reliable and affordable biomarker-based assays with high sensitivity and specificity for the detection of this cancer are a clinical need. With the aim of studying the potential of the plasma-derived extracellular vesicles (EVs), we carried out quantitative proteomic analysis of the EV proteins, using three types of controls and various stages of the disease, which led to the identification of 86 proteins with altered abundance. These include 29 proteins unique to early stage, 44 unique to the advanced stage and 13 proteins being common to both the stages. Many proteins are functionally relevant to the tumor condition or have been also known to be differentially expressed in GBC tissues. Several of them are also present in the plasma in free state. Clinical verification of three tumor-associated proteins with elevated levels in comparison to all the three control types-5'-nucleotidase isoform 2 (NT5E), aminopeptidase N (ANPEP) and neprilysin (MME) was carried out using individual plasma samples from early or advanced stage GBC. Sensitivity and specificity assessment based on receiver operating characteristic (ROC) analysis indicated a significant association of NT5E and ANPEP with advanced stage GBC and MME with early stage GBC. These and other proteins identified in the study may be potentially useful for developing new diagnostics for GBC.

Laparoscopic versus open surgery for the management of post-cholecystectomy benign biliary strictures.

BACKGROUND AND AIM: Surgical management by a bilioenteric anastomosis is the standard for the repair of post-cholecystectomy benign biliary strictures (BBS). This is traditionally done as an open operation. There are a few reports describing the procedure by a laparoscopic technique. The aim of the present study was to describe our experience of laparoscopic bilio-enteric anastomosis [Roux-en-Y hepaticojejunostomy (LRYHJ)/laparoscopic hepaticoduodenostomy (LHD)] in the management of post-cholecystectomy BBS and compare the outcomes with our patients operated by the open approach. METHODS: Retrospective analysis of prospective data of post-cholecystectomy BBS patients treated by laparoscopic bilio-enteric anastomosis. The outcomes were compared with patients who underwent an open repair. RESULTS: Between January 2016 and February 2019, 63 patients underwent surgery for post-cholecystectomy BBS. Twenty-nine patients who underwent laparoscopic bilio-enteric anastomosis (LRYHJ-13, LHD-16) were compared with 34 patients who underwent an open repair. The median age (40 vs 39) years, type of index surgery [laparoscopic cholecystectomy (13 vs 15), laparoscopic converted to open cholecystectomy (10 vs 16), and open cholecystectomy (6 vs 3)], type of injury low stricture (7 vs 5) and high stricture (22 vs 29), preoperative biliary fistula (23 vs 30), and time from injury to repair (6 vs 7 months) were similar in the 2 groups. The median duration of surgery was also similar (210 vs 200 min, p = 0.937); however, the median intraoperative blood loss (50 mL vs 200 mL, p = 0.001), time to resume oral diet (2 vs 4 days p = 0.023),** and median duration of postoperative hospital stay (6 vs 8 days, p = 0.001) were significantly less in the laparoscopy group. Overall morbidity rate (within 30 days post-surgery) was significantly higher in the open repair group (38% vs 20%). In a subgroup analysis of the laparoscopic repair group, the operative time in patients who underwent an LHD was significantly less than LRYHJ (190 vs 230 min, p = 0.034). The other parameters like the mean intraoperative blood loss, time to initiate oral diet, duration of postoperative hospital stay, and incidence of postoperative bile leak were similar. Patients undergoing open repair had a median follow-up of 26 months with two developing anastomotic stenosis and those undergoing laparoscopic repair had a median follow-up for 9 months with one developing anastomotic stenosis. CONCLUSION: Laparoscopic surgery for post-cholecystectomy BBS with an LRYHJ or LHD is feasible and safe and compares favourably with the open approach.

Use of single-lumen tube for minimally invasive and hybrid esophagectomies with prone thoracoscopic dissection: case series.

Minimally invasive and hybrid minimally invasive esophagectomy (MIE) is a technically challenging procedure. Anesthesia for the same is equally challenging due to special requirements of the video-assisted thoracoscopic technique used and shared operative and respiratory fields. Standard ventilatory strategy for this kind of surgery has been 1-lung ventilation with the help of a double-lumen tube. Prone positioning for thoracoscopic dissection facilitates gravity-dependant collapse of the operative side lung induced by a unilateral capnothorax, thus making the use of single-lumen endotracheal tube a feasible option for this surgery. We report our experience of 10 consecutive cases of minimally invasive esophagectomy conducted in prone position at our center and the use of single-lumen endotracheal tube for ventilation.

Minimally invasive oesophagectomy in prone versus lateral decubitus position: A comparative study.

BACKGROUND: Thoracoscopic oesophageal mobilisation during a minimally invasive oesophagectomy (MIE) is most commonly performed with the patient placed in the lateral decubitus position (LDP). The prone position (PP) for thoracoscopic oesophageal mobilisation has been proposed as an alternative. MATERIALS AND METHODS: This was a retrospective, comparative study designed to compare early outcomes following a minimally invasive thoracolaparoscopic oesophagectomy for oesophageal cancer in LDP and in PP. RESULTS: During the study period, between January 2011 and February 2014, 104 patients underwent an oesophagectomy for cancer. Of these, 42 were open procedures (transhiatal and transthoracic oesophagectomy) and 62 were minimally invasive. The study group included patients who underwent thoracolaparoscopic oesophagectomy in LDP (n = 23) and in PP (n = 25). The median age of the study population was 55 (24-71) years, and there were 25 males. Twenty-one (21) patients had tumours in the middle third of the oesophagus, 24 in the lower third, and 3 arising from the gastro-oesophageal junction. The most common histology was squamous cell cancer (85.4%). The median duration of surgery was similar in the two groups; however, the estimated median intraoperative blood loss was less in the PP group [200 (50-400) mL vs 300 (100-600) mL; P = 0.01)]. In the post-operative period, 26.1% patients in the LDP group and 8% in the PP group (8%) developed respiratory complications. The incidence of other post-operative complications, including cervical oesophagogastric anastomosis, hoarseness of voice and chylothorax, was not different in the two groups. The T stage of the tumour was similar in the two groups, with the majority (37) having T3 disease. A mean of 8 lymph nodes (range 2-33) were retrieved in the LDP group, and 17.5 (range 5-41) lymph nodes were retrieved in the PP group (P = 0.0004). The number of patients with node-positive disease was also higher in the PP group (19 vs 10, P = 0.037). CONCLUSION: MIE in the PP is an effective alternative to LDP. The exposure obtained is excellent even without the need for a complete lung collapse, thereby obviating the need for a double-lumen endotracheal tube. A more meticulous dissection can be performed resulting in a higher lymph nodal yield.

Signet ring cell neuroendocrine tumor liver with mesenteric metastasis: Description of a rare phenomenon, with literature review.

Primary hepatic signet ring cell neuroendocrine tumor (NET) is extremely rare, and may show both neuroendocrine and glandular differentiation. Unlike the usual signet ring cells of adenocarcinoma, these cells are characterized by mucin negative, cytokeratin and chromogranin positive intracytoplasmic vacuoles resembling signet ring cells. These tumors are usually well demarcated surgically resectable lesions. To the best of our knowledge, we report the fifth case of primary hepatic signet ring cell NET, with the present case bearing multiple hepatic space occupying lesions and mesenteric metastasis. Due to very few isolated reports, prognosis of NET with signet ring cell morphology is largely unknown. Documentation of this case with review of related literature may enrich the existing knowledge regarding the outcome and management of this rare tumor.

Prompt Repair of Post Cholecystectomy Bile Duct Transection Recognized Intraoperatively and Referred Early: Experience from a Tertiary Care Teaching Unit.

Postcholecystectomy bile duct injuries are a cause of significant morbidity and occasional mortality. Intraoperative recognition and repair of complete biliary transection with hepaticojejunostomy is the recommended treatment; however, it is possible only in few patients as either the injury is not recognized intraoperatively or the center is not geared up to perform an urgent hepaticojejunostomy in these patients with a nondilated duct. Retrospective analysis of data from a tertiary care referral center over a period of 10 years from January 2000 to December 2009 to report the feasibility and outcomes of prompt repair was done (defined as repair within 72 h of index operation) of postcholecystectomy bile duct injury. Ten patients of postcholecystectomy bile duct injury detected intraoperatively and referred early underwent prompt repair. All patients had a complete transection of the bile duct (type of injuries as per Strasberg classification: Type E V: 1, Type E III: 5, Type E II: 3 and Type E I: 1). The mean duration between injury and bile duct repair in the form of Roux-en-Y hepaticojejunostomy (RYHJ) was 22.7 (range 5-42) hours. The mean diameter of the anastomosis was 1.63 (range1-2.1) cm, and the anastomosis was stented in 7 patients. The mean duration of surgery was 4.6 +1.7 h. One patient developed bile leak on the first postoperative day, which settled by day 5. The mean duration of hospital stay was 5.1 (range 4-8) days. With a mean follow-up of 42 (range 24-110) months, all patients had excellent (70 %) or good outcome (30 %). Prompt RYHJ (within first 72 h) for postcholecystectomy biliary transection is an effective treatment and potentially limits the morbidity to the patient.

Minimally invasive versus the conventional open surgical approach of a radical cholecystectomy for gallbladder cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic surgery has traditionally been contraindicated for the management of gall bladder cancer (GBC). This study was undertaken to determine the safety and feasibility of a laparoscopic radical cholecystectomy (LRC) for GBC and compare it with an open radical cholecystectomy (ORC). METHODS: Retrospective analysis of primary GBC patients (with limited liver infiltration) and incidental GBC (IGBC) patients (detected after a laparoscopic cholecystectomy) who underwent LRC between June 2011 and October 2013. Patients who fulfilled the study criteria and underwent ORC during the same period formed the control group. RESULTS: During the study period, 147 patients with GBC underwent a radical cholecystectomy. Of these, 24 patients (primary GBC- 20, IGBC - 4) who underwent a LRC formed the study group (Group A). Of the remaining 123 patients who underwent ORC, 46 matched patients formed the control group (Group B). The median operating time was higher in Group A (270 versus 240 mins, P = 0.021) and the median blood loss (ml) was lower (200 versus 275 ml, P = 0.034). The post-operative morbidity and mortality were similar (P = 1.0). The pathological stage of the tumour in Group A was T1b (n = 1), T2 (n = 11) and T3 (n = 8), respectively. The median lymph node yield was 10 (4-31) and was comparable between the two groups (P = 0.642). During a median follow-up of 18 (6-34) months, 1 patient in Group A and 3 in Group B developed recurrence. No patient developed a recurrence at a port site. CONCLUSION: LRC is safe and feasible in selected patients with GBC, and the results were comparable to ORC in this retrospective comparison.

Role of routine 16b1 lymph node biopsy in the management of gallbladder cancer: an analysis.

BACKGROUND: Involvement of the 16b1 (interaortocaval) lymph node (LN) in gallbladder cancer (GBC) is considered to represent metastatic disease. Although this is universally accepted, the role of routine frozen-section histopathological examination (HPE) of the 16b1 LN in the management of GBC has not been previously reported. METHODS: A prospective study (August 2009-November 2011) using routine biopsy of 16b1 LNs and frozen-section HPE prior to radical resection in patients deemed operable on preoperative evaluation and staging laparoscopy was carried out. RESULTS: Of the 451 GBC patients assessed, 251 (55.7%) were deemed operable on preoperative imaging. Of these, 68 (27.1%) were found to have disseminated disease on staging laparoscopy/laparotomy. Of the 183 patients in whom 16b1 LN biopsy was performed, 34 (18.6%) had evidence of metastases on frozen-section HPE and the planned surgical resection was abandoned (Group A). Of the remaining 149 patients (Group B), 142 (95.3%) underwent curative resection and seven (4.7%) were found to be unresectable as a result of locoregionally advanced disease. A comparison of findings in Group A with those in Group B showed no significant difference in the clinical stage of the tumour. The proportions of patients with jaundice, elevated carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels were significantly higher in Group A than in Group B (P = 0.008, P = 0.012 and P = 0.023, respectively). CONCLUSIONS: Routine 16b1 LN biopsy prevented non-therapeutic radical resection and its associated morbidity in 18.6% of patients deemed resectable on preoperative imaging and staging laparoscopy. The yield was higher in patients with jaundice and elevated preoperative tumour marker levels.

Liver necrosis following corrosive ingestion.

We describe a rare sequel of corrosive ingestion. In this patient, ingestion of a corrosive led to ischemic necrosis of the entire left lobe of the liver (segments II, III, and IV) in addition to causing full-thickness necrosis of the esophagus/stomach, infarction of the spleen, and injury to the left hemidiaphragm. Solid organ involvement following corrosive ingestion is uncommon. Although involvement of the spleen and pancreas from extension of corrosive burns from the adjacent stomach is occasionally described, involvement of the liver following corrosive ingestion has not been reported in the literature till date.

Squamous variant of gallbladder cancer: is it different from adenocarcinoma?

BACKGROUND: Literature on squamous variants of gallbladder cancer (GBC) is limited. METHODS: This was a retrospective analysis of GBC patients operated on between August 2009 and March 2012. Patients with adenosquamous carcinoma or squamous cell carcinoma were compared with adenocarcinoma for clinicopathologic features and surgical outcomes. RESULTS: Of the primary GBC patients resected with curative intent, 14 had adenosquamous carcinoma (10) or squamous cell carcinoma (4) (group A), whereas 122 had adenocarcinoma (group B). Abdominal pain was the most common symptom in both groups; however, presentation with vomiting and an abdominal lump was more common in group A (P = .04 and <.01, respectively). Group A had a significantly larger tumor size (7.9 vs 4.8 cm, P = .01) and a higher incidence of adjacent organ involvement requiring extended resections (85.7% vs 26.2%, P < .01). Despite the higher T stage, node-negative disease was significantly higher in group A (42.9% vs 17.2%, P = .03). There was no significant difference in the median survival after curative resection between the 2 groups (28 vs 31 months, P = .24). CONCLUSIONS: The squamous variant of GBC presented at an advanced T stage; however, nodal involvement and distant metastasis were less common. Despite the higher T stage, curative resection could be achieved in the majority with a comparable survival.

Total laparoscopic esophageal bypass using a colonic conduit for corrosive-induced esophageal stricture.

BACKGROUND: The colon and the stomach are the most commonly used conduits for esophageal replacement in patients with esophageal strictures resulting from corrosive ingestion. The replacement surgeries have traditionally been performed by an open approach. While laparoscopic replacement surgery using a stomach conduit has been previously reported, a total laparoscopic bypass using a colonic conduit has not been previously described. We herein describe the surgical technique and results of laparoscopic esophageal bypass using a colonic conduit. METHODS: Patients with corrosive stricture involving the esophagus with the proximal level at the hypopharynx, or those with concomitant gastric scarring, were selected. The surgery was performed with the patient in a supine position using five abdominal ports and a hockey stick/transverse skin crease neck incision. The main steps include colonic mobilization and assessment of the adequacy of the marginal vascular arcade, creation of a retrosternal tunnel, preparation of the colonic conduit, neck dissection, delivery of the colonic conduit into the neck and cervical pharyngo/esophagocolic anastomosis, and intra-abdominal cologastric and ileocolic anastomosis. RESULTS: During the study period, 39 patients with corrosive stricture of the esophagus were managed surgically at our center with either gastric or colonic bypass. Of these, 22 patients underwent an open procedure (12 retrosternal colonic bypasses and 10 retrosternal gastric bypasses) and 17 patients underwent a laparoscopic procedure (13 retrosternal gastric bypasses and 4 retrosternal colonic bypasses). Patients with stricture at the hypopharynx (n = 2) or those in whom the stomach was contracted (n = 2) were considered for a laparoscopic esophagocoloplasty. The average duration of surgery of these latter four patients was 370 (380, 320, 360, and 420) min and the mean estimated blood loss was 100 mL. All patients could be ambulated on the first postoperative day and were allowed oral liquids by the 7th postoperative day. Compared with patients who underwent an open colonic bypass, there was significantly less need for analgesics. At a median follow-up of 5 (range 3-6) months, all patients are euphagic to solid diet and have excellent cosmetic results. CONCLUSION: Laparoscopic colonic bypass is an achievable, safe, and effective procedure for the management of corrosive strictures of the esophagus.

Mass-forming xanthogranulomatous cholecystitis masquerading as gallbladder cancer.

BACKGROUND: Mass-forming xanthogranulomatous cholecystitis (XGC), an uncommon inflammatory pathology of gallbladder (GB), masquerades as gallbladder cancer (GBC) and diagnosis is often a histological surprise. METHODS: A retrospective analysis of prospectively collected database of patients with GB mass operated between August 2009 and September 2012 was conducted to determine clinical, radiological, and intraoperative findings that might aid in the preoperative diagnosis of mass-forming XGC and ascertain their optimal management strategy. RESULTS: Of the 566 patients with GB mass and suspected GBC, 239 were found to be inoperable on preoperative workup and 129 patients had unresectable disease on staging laparoscopy/laparotomy. Of the 198 with resectable disease, 31 were reported as XGC on final histopathology (Group A), while 167 were GBC (Group B). Of these 31 patients, six with an intraoperative suspicion of benign pathology underwent cholecystectomy with segments IVb and V resection, and frozen section histopathology. Twenty-five underwent radical cholecystectomy, with (n = 10) or without (n = 15) adjacent organ resection. In comparison, anorexia and weight loss were significantly more in Group B (p = 0.001 and <0.001). Intraoperatively, empyema and associated gallstones were more common in Group A (p = 0.011 and <0.001). On computed tomography (CT) of the abdomen, continuous mucosal line enhancement and intramural hypodense bands were significantly more in Group A (p < 0.001 and 0.025). While CT abdomen revealed one or more features suggestive of XGC in 64.5 % (20/31) of patients in Group A, 11(35.5 %) did not have any findings suggestive of XGC on imaging. CONCLUSION: Mass-forming XGC mimics GBC, making preoperative and intraoperative distinction difficult. While imaging findings can help in suspecting XGC, definitive diagnosis require histopathological examination. Presence of typical radiological findings, however, can help in avoiding extended radical resection in selected cases.

A modified minimally invasive technique for the surgical management of large trichobezoars.

BACKGROUND: Trichobezoar which were traditionally managed by open surgical retrieval are now often managed by minimally invasive surgical approach. Removal of a large trichobezoar by laparoscopy, however, needs an incision (usually 4-5 cm in size) for specimen removal and has the risk of intra-peritoneal spillage of hair and inspissated secretions. MATERIALS AND METHODS: The present paper describes a modified laparoscopy-assisted technique with temporary gastrocutaneopexy for the effective removal of a large trichobezoar using a camera port and a 4-5 cm incision (which is similar to that needed for specimen removal during laparoscopy). RESULTS: Three patients with large trichobezoar were managed with the described technique. The average duration of surgery was 45 (30-60) min and the intraoperative blood loss was minimal. There was no peritoneal spillage and the trichobezoar could be retrieved through a 4-5 cm incision in all patients. All had an uneventful recovery and at a median followup of 6 months had excellent cosmetic and functional results. CONCLUSION: The described technique is a minimally invasive alternative for trichobezoar removal. There is no risk of peritoneal contamination and the technical ease and short operative time in addition to an incision limited to size required for the specimen removal, makes it an attractive option.

Laparoscopic esophagogastroplasty: a minimally invasive alternative to esophagectomy in the surgical management of megaesophagus with axis deviation.

INTRODUCTION: The results of cardiomyotomy in patients of achalasic megaesophagus with axis deviation are not satisfactory, and several authors have advocated an esophagectomy in these patients. We describe the technical details and outcomes of a novel technique of laparoscopic esophagogastroplasty for end-stage achalasia. METHODS: Patients with end-stage achalasia, characterized by tortuous megaesophagus were selected. The surgery was performed in supine position using five abdominal ports. The steps included mobilization of the gastroesophageal junction and lower intrathoracic esophagus, straightening and anchoring the pulled intrathoracic esophagus into the abdomen, and a side-side esophagogastroplasty. RESULTS: Four patients with megaesophagus due to end-stage achalasia underwent this procedure. The average duration of surgery was 177.5 (range, 120-240) min. All patients could be ambulated on the first postoperative day. Oral feeding was initiated by the third postoperative day, and all patients had significant improvements in their dysphagia scores. All patients had excellent cosmetic results and were discharged by the fifth postoperative day. An upper gastrointestinal contrast study done at 6 weeks after surgery did not show any hold up of contrast, and there was decrease in the convolutions and diameter of the esophagus. At a mean follow-up of 10.5 (range, 3-15) months, all patients are euphagic without significant symptoms of gastroesophageal reflux. CONCLUSIONS: Laparoscopic esophagogastroplasty is an effective option for relieving dysphagia in megaesophagus due to achalasia with axis deviation and is a reasonable alternative before subjecting to a major and potentially morbid esophagectomy.

Gallbladder cancer management impacted by coexistent tuberculosis.

BACKGROUND: In endemic areas, gallbladder cancer (GBC) and tuberculosis may coexist. This study aimed to ascertain the impact of coexistent tuberculosis on the management of patients with GBC. METHODS: Data of patients with proven GBC with coexistent tuberculosis managed at our centre between January 2003 and December 2007 were analysed from a prospective gallbladder cancer database to highlight the management issues and ascertain the impact that coexistent tuberculosis had on the outcome in these patients. RESULTS: Of the 340 patients of GBC evaluated at our centre, 7 patients had concomitant tuberculosis and constituted the study group. All the patients were women (mean age 56.3 years). The commonest presenting symptoms were abdominal pain, decreased appetite and significant weight loss. Two patients were found to have tuberculosis on preoperative evaluation on a fine-needle aspiration cytology from the left supraclavicular lymph nodes; 3 patients were detected intraoperatively (1 had peritoneal tuberculosis on staging laparoscopy and 2 had tubercular lymphadenitis on interaortocaval lymph node sampling) and 2 were detected postoperatively with histopathological examination showing GBC with tubercular lymphadenitis of the hepatoduodenal lymph nodes. Six of these 7 patients underwent surgery with curative intent and 1 underwent a surgical bypass. CONCLUSION: Five of the 7 patients of GBC with coexistent tuberculosis could have been denied the chance of curative surgery had a preoperative/intraoperative biopsy confirmation not been done. Thus, histopathological confirmation is mandatory before labelling a cancer as metastatic and denying the patient a chance for cure.

Primary Malignant Melanoma of the Esophagus.

Primary malignant melanoma of the esophagus is an extremely rare neoplasm arising from the esophageal mucosal melanocytes. We herein describe a patient of primary malignant melanoma of the esophagus, who was managed by thoracolaparoscopic esophagectomy.

The role of staging laparoscopy in primary gall bladder cancer--an analysis of 409 patients: a prospective study to evaluate the role of staging laparoscopy in the management of gallbladder cancer.

OBJECTIVE: To evaluate the role of staging laparoscopy (SL) in the management of gallbladder cancer (GBC). METHODS: A prospective study of primary GBC patients between May 2006 and December 2011. The SL was performed using an umbilical port with a 30-degree telescope. Early GBC included clinical stage T1/T2. A detectable lesion (DL) was defined as one that could be detected on SL alone, without doing any dissection or using laparoscopic ultrasound (surface liver metastasis and peritoneal deposits). Other metastatic and locally advanced unresectable disease qualified as undetectable lesions (UDL). RESULTS: Of the 409 primary GBC patients who underwent SL, 95 had disseminated disease [(surface liver metastasis (n = 29) and peritoneal deposits (n = 66)]. The overall yield of SL was 23.2% (95/409). Of the 314 patients who underwent laparotomy, an additional 75 had unresectable disease due to surface liver metastasis (n = 5), deep parenchymal liver metastasis (n = 4), peritoneal deposits (n = 1), nonlocoregional lymph nodes (n = 47), and locally advanced unresectable disease (n = 18), that is, 6-DL and 69-UDL. The accuracy of SL for detecting unresectable disease and DL was 55.9% (95/170) and 94.1% (95/101), respectively. Compared with early GBC, the yield was significantly higher in locally advanced tumors (n = 353) [25.2% (89/353) vs 10.7% (6/56), P = 0.02]. However, the accuracy in detecting unresectable disease and a DL in locally advanced tumors was similar to early GBC [56.0%, (89/159) and 94.1%, (89/95) vs 54.6% (6/11) and 100% (6/6), P = 1.00]. CONCLUSIONS: In the present series with an overall resectability rate of 58.4%, SL identified 94.1% of the DLs and thereby obviated a nontherapeutic laparotomy in 55.9% of patients with unresectable disease and 23.2% of overall GBC patients. It had a higher yield in locally advanced tumors than in early-stage tumors; however, the accuracy in detecting unresectable disease and a DL were similar.