Safety and Efficacy of Surgery for Metastatic Tumor to the Pancreas: A Single-Center Experience

Round 1

Reviewer 1 Report

The authors performed a review on the history and role of laparoscopic approach for gallbladder cancer. This area in surgery is not so well developed  . I enjoyed the overall reading of the manuscript.

The abstract is well written, containing a short introduction, an overview of the role of laparoscopic surgery followed by the role of laparoscopic surgery in gallbladder cancer.

The core manuscript is divided in introduction, tumor staging of gallbladder carcinoma, application of laparoscopic technique in surgery, laparoscopic surgery in gallbladder carcinoma, gallbladder carcinoma and robotic surgery, enhanced recovery after surgery and laparoscopic surgery for gallbladder carcinoma and conclusions.

Each section is well written, with a good use of english and has managed to keep me interested throughout reading. The authors cite all major articles pertaining to the subject and the review itself uses 99 citations, which shows the amount of work put into the article. The conclusions are supported by the text.

I would have liked to also see a section on the diagnosis of gallbladder cancer and a section on surgical technique.

Author Response

The suggestions of this reviewer refer to other paper regarding laparoscopic approach to gallbladder cancer. We obviously think that this is a mistake.

Reviewer 2 Report

1.     The manuscript entitled, “Safety and efficacy of surgery for metastatic tumor to the pancreas: a single-center experience” is written in a way that it has a bad Results section but a good Discussion section. Specifically, the Results section is written in a way as if the authors are just trying to list everything that they experienced, without much interpretation. What is missing for the readers and reviewers is the critical analysis or perspective to tie everything together. It is hard to read and follow because the result just feels like a dump of all the information. It will be helpful if the authors can organize the Results section in some subheadings and find a logical and easy to follow order to specify the results.

 

2.     The novelty of the manuscript is definitely low. But for clinicians to make an informed decision, more reports supporting similar outcomes are always good.

 

3.     Provide details of what statistics were used for each table (if same) or for each variable (if different). There are many variables, where the standard deviation are high, such that the error bars would overlap completely between the two groups, but the p-value shown is less than 0.05 and is reported as statistically significant.

 

4.     The authors mentioned in the Results section that “Compared with patients, who had other primary tumors, those with metastases from RCC often presented with multiple PM”. They also mention that “Total pancreatectomy was reserved for patients with multiple PM”. Could it be that the better prognosis of mRCC patients with PM is because they are undergoing total pancreatectomy? Could it be that removing the entire pancreas is safer than resecting just a part of the pancreas?

 

5.     In Figure 2, use different coloured arrows/arrowheads to show hypovascular lesion of the pancreatic head, bile duct and panceatic duct dilation.

 

Author Response

1. The manuscript entitled, “Safety and efficacy of surgery for metastatic tumor to the pancreas: a single-center experience” is written in a way that it has a bad Results section but a good Discussion Specifically, the Results section is written in a way as if the authors are just trying to list everything that they experienced, without much interpretation. What is missing for the readers and reviewers is the critical analysis or perspective to tie everything together. It is hard to read and follow because the result just feels like a dump of all the information. It will be helpful if the authors can organize the Results section in some subheadings and find a logical and easy to follow order to specify the results.

 

We thank the Reviewer for the observation. As suggested by the Reviewer, we have revised the Results section and added subheadings in order to make it easier to read. Furthermore, we have changed the first paragraph of the Results section to make it more straightforward. All changes can be found in the revised form of the manuscript in yellow.

 

2. The novelty of the manuscript is definitely low. But for clinicians to make an informed decision, more reports supporting similar outcomes are always good.

 

We would like to thank the Reviewer for his insight as we agree with his comment.

 

3. Provide details of what statistics were used for each table (if same) or for each variable (if different). There are many variables, where the standard deviation are high, such that the error bars would overlap completely between the two groups, but the p-value shown is less than 0.05 and is reported as statistically significant.

 

Thank you very much for this suggestion. We have added a caption to each table, providing details of the statistical analysis which was used for the different variables. Categorical variables were analyzed with Chi square test, with the exception of variables with absolute frequencies <5 which were analyzed with Fisher exact test (i.e. preoperative diabetes). Quantitative variables (once verified that they are not normally distributed) were compared with Mann-Whitney test. We have also reviewed the results reported in Table 1 and 3, and we have noticed that we have wrongly reported the size of PM and the duration of surgical operation as mean ± standard deviations. We have corrected the Tables by reporting the correct values as median (range) and repeated the statistical analysis with Mann-Whitney test. Correct data are reported in yellow in Table 1 and 3 of the revised form of the manuscript.

 

4. The authors mentioned in the Results section that “Compared with patients, who had other primary tumors, those with metastases from RCC often presented with multiple PM”. They also mention that “Total pancreatectomy was reserved for patients with multiple PM”. Could it be that the better prognosis of mRCC patients with PM is because they are undergoing total pancreatectomy? Could it be that removing the entire pancreas is safer than resecting just a part of the pancreas?

 

We thank the Reviewer for this comment. As we stated in the Discussion section, the type of surgical procedure is another controversial aspect in the treatment of PM. Bassi et al reported a 29% rate of pancreatic recurrences after performing atypical resections in cases of metastases from RCC. It is unclear whether such recurrences after atypical resections are due to an inadequate surgical procedure or to undetected multifocality. Multiple lesions are not rare, particularly in patients with metastases from RCC. One third of our patients presented with multiple PM, and more than half of cases with metastatic RCC had multiple pancreatic lesions. However, total pancreatectomy represents a surgical procedure with two major metabolic drawbacks. First, glycemic instability which requires insulin replacement therapy and second, a complete exocrine insufficiency which leads to steatorrhea, often difficult to handle. Considering the indolent behavior of PM from RCC, it would seem wise to check carefully for multiple pancreatic lesions in order to choose the most appropriate surgical approach (standard oncologic resection vs atypical approaches vs total pancreatectomy). As a matter of fact, the choice between standard and atypical resections is probably unimportant providing the resection margins obtained are cancer-free. In order to highlight this issue as recommended by the Reviewer, we have added the following sentence to the Discussion section: “In our case series, among patients with PM from renal cell cancer, only one patient required a total pancreatectomy while in all other cases we tailored the surgical approach according to a careful intraoperative evaluation of the pancreatic parenchyma”

 

5. In Figure 2, use different coloured arrows/arrowheads to show hypovascular lesion of the pancreatic head, bile duct and panceatic duct dilation.

 

Thank you. We have added two more red arrows to show the bile duct and pancreatic duct dilation in addition to the yellow arrow indicating the hypovascular pancreatic head lesion. 

Reviewer 3 Report

The metastases to the pancreas are rare findings, and there is no consensus about the potential role of the surgery in these cases. The MS evaluates the surgically treated metastases, providing an excellent study. The statistical methods, the presentation, the references are correctly written, only one questionable issue is raised. In the Abstract and in the Table 1. the authors mention 44 patients, however, the Material and Methods section says just about 37 pts. This contradiction should be clarified. I suppose that only 37 patients have been operated, while the rest were treated by other ways. Is this approach correct? If yes, this should be clearly explained, together with the other treatment options (if any). 

Author Response

1. The metastases to the pancreas are rare findings, and there is no consensus about the potential role of the surgery in these cases. The MS evaluates the surgically treated metastases, providing an excellent study. The statistical methods, the presentation, the references are correctly written, only one questionable issue is raised. In the Abstract and in the Table 1. the authors mention 44 patients, however, the Material and Methods section says just about 37 pts. This contradiction should be clarified. I suppose that only 37 patients have been operated, while the rest were treated by other ways. Is this approach correct? If yes, this should be clearly explained, together with the other treatment options (if any). 

 

 

We thank the Reviewer for his comment and for his observations. In this study we observed 44 patients, and among these, 37 received a surgical approach. In order to better clarify this issue, we have added the following sentence in the Methods section “During this time interval, we observed 44 patients with PM and among these, 37 underwent a surgical procedure”.

Furthermore, we have added the following sentence in the Results section: “Among the seven patients who did not received a surgical approach, two refused surgery, while the other five cases had either a metastatic spread or a locally advanced tumor. Four of them received palliative chemotherapy while one case with PM from RCC was treated with a multi-targeted receptor tyrosin kinase inhibitor”.